Systems and methods for bioimpedance body composition measurement

ABSTRACT

There is provided a system for monitoring a heart of a subject and monitoring impedance-related parameters, comprising: a feeding tube, an electrode disposed(s) on a distal end of the feeding tube, a controller that performs, while the feeding tube is in located in an esophagus and feeding is delivered to a subject via the feeding tube, in a plurality of iterations: continuously measuring voltage at the electrode(s) of the feeding tube, applying alternating current(s) between the electrode(s) of the feeding tube and at least one other electrode, computing impedance measurement(s) from the electrode(s) of the feeding tube according to the applied alternating current(s) and the measured voltage, computing impedance-related parameter(s) based on the impedance measurement(s), terminating the application of the alternating current(s), obtaining an electrocardiogram (ECG) measurement based on the voltage measured at the electrode(s) of the feeding tube, and providing the impedance-related parameter(s) and the ECG measurement.

RELATED APPLICATIONS

This application is a Continuation-in-Part (CIP) of PCT PatentApplication No. PCT/IL2019/051210 having International filing date ofNov. 5, 2019, which claims the benefit of priority under 35 USC § 119(e)of U.S. Provisional Patent Application No. 62/755,650 filed on Nov. 5,2018. The contents of the above applications are all incorporated byreference as if fully set forth herein in their entirety.

FIELD AND BACKGROUND OF THE INVENTION

The present invention, in some embodiments thereof, relates to bodycomposition measurement and, more specifically, but not exclusively, tosystems and methods for measurement of body composition using impedancemeasurements.

Body composition measurement is a valuable tool for example, forassessing nutritional status and/or physical fitness in a variety ofclinical settings.

The most commonly used methods to assess body composition in vivo aredual-energy X-ray absorptiometry (DXA), computerized tomography (CT),and magnetic resonance imaging (MRI). Although these imaging methods areaccurate in measuring body composition, their practical use is limited(e.g., for routine measurements), for example, because of high cost,large amount of time needed to perform measurement (e.g., to acquire MRIimages), and radiation exposure in CT and/or DXA. Therefore,bioelectrical impedance measurement, which are low cost, fast, and donot expose the patient to radiation, are increasingly being implementedfor monitoring of patients and for nutritional management and control ofpatients muscle mass and hydration status in the ICU.

SUMMARY OF THE INVENTION

According to a first aspect, a system for monitoring a heart of asubject and monitoring parameters based on impedance measurements of thesubject, comprises: a feeding tube for insertion into a distal end of anesophagus of the subject, at least one electrode disposed on a distalend of the feeding tube at a location such that at least one electrodeis located at the distal end of the esophagus of the subject when inuse, a controller that performs, while the feeding tube is in located inthe esophagus and feeding is delivered to the subject via the feedingtube, in a plurality of iterations: continuously measuring voltage atthe at least one electrode of the feeding tube, applying at least onealternating current between the at least one electrode of the feedingtube and at least one other electrode, computing at least one impedancemeasurement from the at least one electrode of the feeding tubeaccording to the applied at least one alternating current and themeasured voltage, computing at least one impedance-related parameterbased on the at least one impedance measurement, terminating theapplication of the at least one alternating current, obtaining anelectrocardiogram (ECG) measurement based on the voltage measured at theat least one electrode of the feeding tube, and providing the at leastone impedance-related parameter and the ECG measurement.

According to a second aspect, a method of monitoring a heart of asubject and monitoring parameters based on impedance measurements of thesubject, comprises: providing a feeding tube for insertion into a distalend of an esophagus of the subject, providing at least one electrodedisposed on a distal end of the feeding tube at a location such that atleast one electrode is located at the distal end of the esophagus of thesubject when in use, while the feeding tube is in located in theesophagus and feeding is delivered to the subject via the feeding tube,in a plurality of iterations: continuously measuring voltage at the atleast one electrode of the feeding tube, applying at least onealternating current between the at least one electrode of the feedingtube and at least one other electrode, computing at least one impedancemeasurement from the at least one electrode of the feeding tubeaccording to the applied at least one alternating current and themeasured voltage, computing at least one impedance-related parameterbased on the at least one impedance measurement, terminating theapplication of the at least one alternating current, obtaining anelectrocardiogram (ECG) measurement based on the voltage measured at theat least one electrode of the feeding tube, and providing the at leastone impedance-related parameter and the ECG measurement.

According to a third aspect, a computer program product for monitoring aheart of a subject and monitoring parameters based on impedancemeasurements of the subject, comprises program instructions which, whenexecuted by a processor, cause the processor to perform, while a feedingtube is in located in a distal end of an esophagus of the subject andfeeding is delivered to the subject via the feeding tube, in a pluralityof iterations: continuously measuring voltage by at least one electrodeof disposed on a distal end of the feeding tube at a location such thatat least one electrode is located at the distal end of the esophagus ofthe subject when in use, applying at least one alternating currentbetween the at least one electrode of the feeding tube and at least oneother electrode, computing at least one impedance measurement from theat least one electrode of the feeding tube according to the applied atleast one alternating current and the measured voltage, computing atleast one impedance-related parameter based on the at least oneimpedance measurement, terminating the application of the at least onealternating current, obtaining an electrocardiogram (ECG) measurementbased on the voltage measured at the at least one electrode of thefeeding tube, and providing the at least one impedance-related parameterand the ECG measurement.

In a further implementation form of the first, and second aspects, thecontroller further performs: analyzing the ECG measurement to determinean indication of cardiac abnormality, and applying via the at least oneelectrode of the feeding tube, an electrical pattern selected fortreating the cardiac abnormality.

In a further implementation form of the first, and second aspects, theat least one electrode of the feeding tube comprises a plurality ofelectrodes, and analyzing comprises analyzing each respective ECGmeasurement by each respective ECG electrode, and wherein the controllerfurther performs: selecting a respective electrical pattern based on theanalysis of each respective ECG measurement, and applying by each of theplurality of electrodes of the feeding tube, the respective electricalpattern for treating the cardiac abnormality.

In a further implementation form of the first, and second aspects, theelectrical pattern is selected from the group consisting of:defibrillation electrical pattern for treating the cardiac abnormalityof ventricular fibrillation (VF) and/or ventricular tachycardia (VT),cardiac pacing electrical pattern for treating the cardiac abnormalityof abnormal heart rate and/or block in electrical conduction in theheart, and cardioversion electrical pattern for treating the cardiacabnormality of cardiac arrhythmia convertible to normal sinus rhythm.

In a further implementation form of the first, and second aspects, theelectrical pattern applied via the at least one electrode of the feedingtube has significantly less power in comparison to an electrical patternapplied via extracorporeal electrodes to a skin surface of a chest ofthe subject.

In a further implementation form of the first, and second aspects, theelectrical pattern applied via the at least one electrode of the feedingtube has a power of less than about 50 Joules when the electricalpattern applied via extracorporeal electrodes is about 100 to 500Joules.

In a further implementation form of the first, and second aspects, theanalyzing the ECG measurements to determine the indication of cardiacabnormality and the application of the electrical pattern are iteratedin the plurality of iterations.

In a further implementation form of the first, and second aspects, thecontroller further performs: in response to the determined indication ofcardiac abnormality, generating instructions for execution by a feedingcontroller for halting the feeding of the subject via the feeding tube,and in response to the execution by the feeding controller for haltingof the feeding, performing the application of the electrical pattern.

In a further implementation form of the first, and second aspects, theat least one impedance-related parameter comprises a body composition ofa body segment located between the at least one electrode of the feedingtube and the at least one other electrode located externally to a bodyof the subject, wherein the controller further performs: analyzing acombination of the ECG measurement and the at body composition todetermine likelihood of a certain cardiac abnormality selected from aplurality of cardiac abnormalities, and applying via the at least oneelectrode of the feeding tube, an electrical pattern selected to treatthe certain cardiac abnormality.

In a further implementation form of the first, and second aspects, thebody composition comprises lung fluid and the body segment comprises alung.

In a further implementation form of the first, and second aspects, theanalyzing the ECG measurements to determine the indication of cardiacabnormality and the application of the electrical pattern are iteratedin the plurality of iterations.

In a further implementation form of the first, and second aspects, theat least one impedance-related parameter comprises at least onebreathing parameter indicative of respiration effort of the subject,wherein the controller further performs: analyzing a combination of theECG measurement and the at least one breathing parameter to determinelikelihood of a combined cardiac abnormality and respiratoryabnormality, and at least one of: (i) applying via the at least oneelectrode of the feeding tube, an electrical pattern selected to treatthe certain cardiac abnormality, and (ii) generating instructions forexecution by a mechanical ventilator that mechanically ventilates thesubject, for adjustment of a mechanical ventilation pattern applied tothe subject for treating the respiratory abnormality.

In a further implementation form of the first, and second aspects, thecontroller further: generates instructions for adapting at least one of:a feeding and a medication by a feeding controller delivered via thefeeding tube according to the ECG measurement.

In a further implementation form of the first, and second aspects, thecontroller further: analyzes the at least one impedance-relatedparameter to detect an indication of gastric reflux in the esophagusoccurring during a time interval, analyzes the ECG measurement to detectlikelihood of no new cardiac abnormality developed during the timeinterval, and generate an indication that differentiates between gastricreflux and cardiac abnormality.

In a further implementation form of the first, and second aspects, theat least one electrode comprises a plurality of spaced apart electrodeslocated on the distal end portion of the feeding tube, wherein obtainingcomprises obtaining a plurality of ECG measurements, each respective ECGmeasurement obtained a respective electrode of the plurality ofelectrodes, wherein each respective ECG measurement denotes a differentorientation relative to a heart of the subject according to therespective location of the respective electrode on the feeding tube,wherein the controller further performs: analyzing the plurality of ECGmeasurements from the plurality of spaced apart electrodes located onthe distal end portion of the feeding tube to determine an indication ofcardiac abnormality, and applying via the plurality of electrodes of thefeeding tube, a selected electrical pattern to treat the cardiacabnormality.

In a further implementation form of the first, and second aspects, thecontroller further performs: analyzing the at least oneimpedance-related parameter of the at least one electrode to identifythat the at least one electrode is in contact with the lower esophagealsphincter (LES) of the subject, wherein the analyzing is performedduring the plurality of iterations for confirming continuous contactbetween the at least one electrode and the LES during the measurementsof the ECG.

In a further implementation form of the first, and second aspects, theat least one electrode comprises a plurality of spaced apart electrodeslocation on the feeding tubes, the position of the plurality of spacedapart electrodes selected to obtain ECG measurements at a plurality oftarget orientations relative to the heart when a certain electrode is incontact with the LES.

In a further implementation form of the first, and second aspects, theat least one other electrodes comprises at least one extracorporealelectrode located externally of a body of the subject for contacting thebody of the subject.

In a further implementation form of the first, and second aspects, theat least one electrode disposed on the distal end of the feeding tubecomprises a plurality of electrodes disposed on the distal end of thefeeding tube, wherein the at least one electrode comprises a firstelectrode of the feeding tube and the at least one other electrodecomprises a second electrode of the feeding tube.

Unless otherwise defined, all technical and/or scientific terms usedherein have the same meaning as commonly understood by one of ordinaryskill in the art to which the invention pertains. Although methods andmaterials similar or equivalent to those described herein can be used inthe practice or testing of embodiments of the invention, exemplarymethods and/or materials are described below. In case of conflict, thepatent specification, including definitions, will control. In addition,the materials, methods, and examples are illustrative only and are notintended to be necessarily limiting.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

Some embodiments of the invention are herein described, by way ofexample only, with reference to the accompanying drawings. With specificreference now to the drawings in detail, it is stressed that theparticulars shown are by way of example and for purposes of illustrativediscussion of embodiments of the invention. In this regard, thedescription taken with the drawings makes apparent to those skilled inthe art how embodiments of the invention may be practiced. In thedrawings:

FIG. 1 is a schematic of a system for measuring body composition in oneor more body portions of a patient by selectively activating electrodesof a certain contact component of multiple contact components connectedby a multi conductor busbar, in accordance with some embodiments of thepresent invention;

FIG. 2 is a flowchart of a computer implemented method for selectivelyactivating electrodes of a certain contact component of multiple contactcomponents connected by a busbar, in accordance with some embodiments ofthe present invention;

FIG. 3 is a schematic depicting an exemplary architecture of anaddressable electrode components, in accordance with some embodiments ofthe present invention;

FIG. 4 is a schematic of an exemplary implementation of two contactcomponent coupled to the same multi conductor busbar, in accordance withsome embodiments of the present invention;

FIG. 5 is a schematic depicting placed contact components, which areindependently addressable over a common multi conductor busbar, formonitoring multiple body segments of a patient, in accordance with someembodiments of the present invention;

FIG. 6 is a schematic based on the setup described with reference toFIG. 5, including an additional contact component with electrodesthereon positioned for measuring of impedance for estimation of cardiacoutput, in accordance with some embodiments of the present invention;

FIG. 7 is a schematic based on the setup described with reference toFIG. 6 (and FIG. 5), including additional contact components located onthe left side of the patient's body, in addition to the contactcomponents positioned on the right side of the patient's body as inFIGS. 5 and 6, in accordance with some embodiments of the presentinvention;

FIG. 8 is a schematic of an architecture in which each contact componentis connected to a main multi conductor busbar via an individual cable,in accordance with some embodiments of the present invention;

FIG. 9 is a schematic of an architecture in which each electrode isconnected to a main multi conductor busbar via an individual cable, inaccordance with some embodiments of the present invention;

FIG. 10 is a schematic depicting an exemplary contact component placedin contact with a skin of a patient for measuring of impedance of a bodysegment including tissue, in accordance with some embodiments of thepresent invention;

FIG. 11 is a schematic depicting an example of a measurement of a wholebody segment and a measurement of a leg segment, to help understand someembodiments of the present invention

FIG. 12 includes Piccoli diagrams for a whole body measurement and for abody segment, to help understand improved accuracy of impedance measuredfor the body segment in comparison to the whole body;

FIG. 13 is a schematic depicting a process of selective activation ofelectrodes of multiple contact components for sensing multiple bodysegments, in accordance with some embodiments of the present invention;

FIG. 14 includes some exemplary BIS equations, in accordance with someembodiments of the present invention;

FIG. 15 includes some exemplary equations for computing exemplary healthparameters, in accordance with some embodiments of the presentinvention;

FIG. 16 is a schematic depicting exemplary presentations based onanalyzed impedance measurements of body segments, in accordance withsome embodiments of the present invention;

FIG. 17 is a schematic of an exemplary presentation of impedance datafor multiple body segments, in accordance with some embodiments of thepresent invention;

FIG. 18 includes a schematic of a cross section of a foot of a patientan inflatable sleeve with electrodes and a schematic of a cross sectionof a foot with electrodes on conductor strips, in accordance with someembodiments of the present invention;

FIG. 19 is a flowchart of an exemplary process of monitoring a heart ofa subject using electrocardiogram (ECG) measurements and/or monitoringimpedance-related parameters and/or treating the subject based on theECG measurements and/or the impedance-related parameters, where the ECGand impedance measurements are obtained from electrodes on a feedingtube positioned in the esophagus, in accordance with some embodiments ofthe present invention;

FIG. 20 is a flowchart of an exemplary process of monitoring a heart ofa subject using ECG measurements and/or monitoring for reflux usingelectrodes located on a feeding tube positioned in the esophagus, inaccordance with some embodiments of the present invention; and

FIG. 21 is a flowchart of an exemplary process of monitoring a heart ofa subject using ECG measurements and/or monitoring for reflux and/ormeasuring body composition using electrodes located on a feeding tubepositioned in the esophagus, in accordance with some embodiments of thepresent invention.

DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION

The present invention, in some embodiments thereof, relates to bodycomposition measurement and, more specifically, but not exclusively, tosystems and methods for measurement of body composition using impedancemeasurements.

An aspect of some embodiments of the present invention relates tosystems, methods, an apparatus, and/or code instructions (e.g., storedon a memory and executable by hardware processor(s)) for obtainingimpedance measurements in one or more body segments of a patient, forexample, for estimating and/or measuring and/or bed side monitoring bodycomposition of the respective body segment clinical studies have shownthat impedance date and other sensory data of patient body parts, form aclear indication of muscle mass, electrolyte concentrations, andhydration status.

The said information can close loop control the nutritional intakeassigned to the treated patient leading to optimal convalescence. Thepatient may be diagnosed, treatment may be planned, and/or the patientmay be treated based on the body composition. Contact component areprovided. The contact components, which are designed for placement onthe patient, optionally on the skin and inside the patient body includemultiple electrodes for contacting the body of the patient. The contactcomponents are separate structures that are not necessarily connected toeach other, apart from a multi conductor busbar which connects two ormore contact components to a controller. Each contact component may beindependently positioned at different locations on the body of thepatient and inside the patient. The busbar is flexible, designed toprovide freedom of motion for each contact component so that the contactcomponents are positionable at spaced apart locations for monitoring ofdifferent body segments. Each contact component and/or each electrode ofeach contact component is associated with a unique address and includesthe corresponding circuits. The controller issues instructions foroperation of the electrodes (e.g., as current injectors, currentreceivers, anodes, cathodes, and/or voltage sensors) over a busbarconnected to multiple contact components (at least two), via arespective unique address of the respective contact component and/orbusbar (e.g., via an address decoder circuit). The controller issuesinstructions for operating a selected pair of contact componentsconnected by a common multi conductor busbar using the respective uniqueaddress, obtains one or more impedance measurements indicative ofimpedance of a body segment located between the pair of contactcomponents, and provides the impedance measurement for estimation ofbody composition of the body segment. The controller may sequentiallyand/or iteratively activate different pairs of contact components forcurrent injection and other electrodes for impedance measuring of bodysegments, for example, for real time monitoring. The method enables forthe examined body part to have two current injecting electrodes andbetween them two voltage sensing electrodes which is the desired 4electrodes approach to impedance sensing yet the two electrodes approachis another embodiment (i.e., pair used for current delivery as well asvoltage sensing).

Optionally, each respective contact component includes three electrodesarranged along a long axis of the respective contact component. Thecontroller operates a middle electrode of each contact component of thepair for injecting the current, and as said operates an inner facingelectrode of each contact component of the pair for voltage measurement.

As used herein the term inner facing electrode refers to the electrodesof the pair of contact components that are closest to one another. Forexample, for a pair of contact components placed on the ankle and chest,the inner facing electrode of the ankle contact component is theelectrode closest to the chest, and the inner facing electrode of thechest contact component is electrode closest to the ankle (e.g., asdepicted by the figures described below).

An aspect of some embodiments of the systems, methods, apparatus, and/orcode instructions described herein use the same electrode(s) located ona feeding tube placed within the esophagus of a subject, optionallywhile feeding is being delivered by the feeding tube, to alternativelyand iteratively measure impedance and obtain ECG measurements. Voltageis continuously sensed at the electrode(s) of the feeding tube. Analternating current is applied between the electrode at the feedingtube, and another electrode (also located on the feeding tube and/or anextracorporeal electrode and/or at another location in the body).Impedance is measured using the applied current and voltage. Theimpedance may be used for computing different parameter for multipleapplications as described herein, for example for computing: bodycomposition measurement, amount of lung fluid, breathing parameters,reflux, and location of the feeding tube. When application of current isstopped, ECG is measured based on the voltage sensed at the electrode(s)of the feeding tube. The ECG may be analyzed to determine a cardiaccondition, for example, arrhythmia. A suitable electrical pattern may beapplied by the same electrode(s) on the feeding tube (and/or otherelectrodes on the feeding tube) to treat the cardiac conditionidentified based on the ECG measured at the electrode(s) on the feedingtube, for example, defibrillation, cardiac pacing, and/or cardioversion.The alternating sensing of impedance and ECG, and optionally thetreatment, may be continuously iterated for continuous monitoring and/ortreatment of the tube fed patient.

At least some implementations of the systems, methods, apparatus, and/orcode instructions described herein address the technical problem and/ormedical problem and/or improve the technical field, of automaticallycontinuously monitoring and/or treating subjects that are fed using afeeding tube, including monitoring ECG measurements and/or impedancemeasurements of the subject while the subject is being fed and/or drugsadministered using the feeding tube and injections. The technicalproblem and/or medical problem may further relate to treating thesubject based on the ECG measurements while the subject is being fedusing the feeding tube. For example, for patient continuous monitoringin the ICU and/or other departments, multiple devices and theirassociated cabling and/or tubing connecting the patient to monitoringconsoles, processors and fluid and vacuum delivery devices are used,which requires a large amount of effort to set up and monitor, and/orincreased risk of error and/or unsafe treatment. to be minimized for thesake of improving the patient environment and creating a safer and moreconvenient surrounding.

At least some implementations of the systems, methods, apparatus, and/orcode instructions described herein improve the technical field and/oraddress the above mentioned technical problem, by a feeding tube withone or more electrodes, and a controller that iteratively terminates anyelectrical current applied via the electrodes for measuring ECG, andactivates the electrodes on the feeding tube and/or drug delivery devicefor applying an electrical pattern for treating a cardiac condition ofthe patient based on the measured ECG and/or for applying an electricalcurrent to the at least one electrode on the feeding tube for measuringimpedance, for example, for detecting reflux and/or biocomposition of abody segment (e.g., lung fluid and/or other measurements, as describedherein). This may reduce the amount of equipment required, increaseaccuracy of the measurements, increase effectiveness of treatment,and/or reduce risk of error.

At least some implementations of the systems, methods, apparatus, and/orcode instructions described herein improve over existing approaches formeasuring ECG and/or treating the patients with electrical patternsbased on the ECG.

For example, in one approach, electrodes on a tube located in theesophagus are designed for passively measuring ECG, and are unable toapply electrical current for treating the ECG and/or for measuringimpedance. In another approach, electrodes on a tube in the esophagusare designed for applying an electrical pattern to treat a cardiaccondition of the patient, based on ECG signals measured outside the bodyof the patient using standard ECG electrodes positioned at standard ECGlocations on the skin of the chest of the patient. Different electrodesare used for ECG sensing and for applying the electrical current fortreating the heart.

In contrast, at least some implementations of the systems, methods,apparatus, and/or code instructions described herein use the sameelectrodes on the feeding tube for sensing ECG and for applying anelectrical pattern for treating a cardiac condition detected based onthe ECG (measured from the same electrodes from which the treatment isapplied) and/or for applying an electrical current for measuring one ormore impedance-related parameters (e.g., reflux, lung fluid, bodycomposition, breathing parameters). This may enable reducing the amountof electrodes applied to the patient, for example, external standard ECGelectrode may not necessarily be required. The amount of devices appliedto the patient may be reduced, for example, different devices to measureECG, reflux, breathing, lung fluid, and/or other body composition. Usinga single set of electrodes on the feeding tube, while the patient isbeing fed, rather than other electrodes and/or devices and/or ratherthan manual intervention, reduces risk of error, for example, due toincorrectly placed devices, missed manual measurements, and/orincorrectly interpreted measurements. When the single set of electrodeson the feeding tube is used in combination with other devices and/orexternal electrodes, the accuracy of the measurements and/oreffectiveness of the treatment may be improved.

Improved electrical treatment may be delivered to treat cardiac problemsof the patient, for example, by combining the ECG data with impedancemeasurements obtained by the same electrodes, for example, a heartproblem that is causing a buildup of fluid in the lungs may be bettertreated. In another example, feeding of the patient may be stoppedand/or adjusted (e.g., reduced rate, different formula) based on thecardiac condition of the patient obtained from the ECG data. In yetanother example, a patient medication condition (e.g., chest pain) maybe determined to be due to reflux rather than to a heart attack byanalyzing the impedance measurement to determine whether reflux ispresent and/or analyzing ECG data to determine whether the patient isexperiencing a heart attack. In yet another example, a mechanicalventilator is adjusted based on a combination of breathing parametersobtained from impedance readings of the electrodes and ECG data obtainedfrom the electrode. All of the previously mentioned examples are usingthe same set of electrodes on the feeding tube, while the patient isbeing fed. In yet another example, the amount of energy delivered by theelectrodes on the feeding tube to treat cardiac abnormalities (e.g.,pacing, defibrillation, inversion) may be significantly lower than theenergy that would otherwise be delivered using standard approaches, byextracorporeal electrodes applied to the surface of the chest of thepatient from outside the body of the patient. For example, less than 50Joules by the electrodes located on the feeding tube in comparison toabout 200-500, or 160-360, or 100-500 Joules of energy by extracorporealelectrodes. The lower energy may be safer for the patient. Moreover,using the existing electrodes on the feeding tube to apply electricalpatterns to treat cardiac conditions determined based on the ECG signalsof the same electrodes reduces time from diagnosis to treatment, sincethe electrical treatment may be provided within a short amount of time(e.g., less than a second, 1-5 seconds) from detection of the cardiaccondition. In contrast, using existing approaches, a large amount oftime may pass from when the abnormal ECG is identified to when externalelectrodes are placed on the chest of the patient (since such electrodesare not placed before a problem is actually encountered) and electricaltreatment is applied.

Optionally, some embodiments relate to using the skin mounted electrodesfor muscle nerve stimulation, optionally by passing low voltage currentthrough muscles (e.g., which may be sore) and/or nerves to enhance theirrecuperation.

At least some implementations of the systems, methods, apparatus, and/orcode instructions described herein relate to the technical problem ofreducing a number of cables and/or conductors for measuring impedance ofdifferent body segments. At least some implementations of the systems,methods, apparatus, and/or code instructions described herein addressthe technical problem by the architecture of the contact components withthree electrodes thereon located along a long axis of the contactcomponent, and the controller that operates the middle electrode as acurrent injector and/or current collector, and operates the inner facingelectrodes as voltage sensors. A certain contact component may be usedto measure impedance of two neighboring segments, for example, for acontact component placed on the trunk of the body, the middle electrodeis operated for current, and the end electrode facing the legs isoperated for sensing voltage of the leg segment, and the electrode onthe other end facing the head is operated for sensing voltage of anupper body segment.

The architecture of the contact component (which includes the triadelectrode arrangement along a line for applying current and measuringvoltage of the applied current) enables monitoring impedance of bodysegment(s) located in one direction of the contact component, and toother body segment(s) located in an opposite direction of the samecontact component by a small number of conductors. For example, for acontact component positioned on the hip, for body segments from the hiptowards the ankle, and other body segments from the hip towards thehead. 3 electrodes of the contact component connected to a common busbarmay be used instead of 4 independent electrodes each connected to itsown pair of cables using standard processes.

The architecture described herein enables positioning the contactcomponents (i.e., electrodes thereon) anywhere on the body of thepatient. A small number of conductors on busbars (e.g., one, two, ormore) connect the multiple contact components, enabling monitoring ofbody segments between any selected pair of contact components byaddressing hence, avoiding the need for individual conductor(s) persensor or electrode.

At least some implementations of the systems, methods, apparatus, and/orcode instructions described herein relate to the technical problem ofimproving measurement of impedance of body segments of a patient. Atleast some implementations of the systems, methods, apparatus, and/orcode instructions described herein address the technical problem by thearchitecture of the contact components with three electrodes thereonlocated along a long axis of the contact component, and the controllerthat operates the middle electrode as a current injector and/or currentcollector, and operates the inner facing electrodes as voltage sensors.Since the current passes between the middle electrodes of the pair ofcontact components, the voltage measured by the inner electrodes of thepair of contact components more accurately measures the voltage dropresulting from the current itself as the current travels past the innerelectrodes on its way to, or coming out from the middle electrodes.

At least some implementations of the systems, methods, apparatus, and/orcode instructions described herein relate to the technical problem ofimproving accuracy of bioelectrical impedance measurements of body partsof a patient. For example, for monitoring patients, such as patients inthe intensive care unit (ICU), which may be at risk of, for example,internal bleeding and/or edema. Such patients may be monitored usingbioelectrical impedance measurement, which is fast becoming an acceptedindication of health status, for example, to detect current bodycomposition, monitor trends of body composition (e.g., getting worse orbetter), and/or predict future body composition. Each of the triad 3elements includes a decoder, switches electrodes and amplifier, the lastone is activated when the specific electrode is assigned as a voltagesensing electrode. The added amplifier will enable the use of lowerinjected current which is always clinically desired, without sacrificinggood S/N.

Bioelectrical impedance analysis for measurement of body composition(e.g., in the ICU) may be performed using bioelectrical impedance vectoranalysis (BIVA). For example, repeated BIVA hydration measurements maydetect fluid accumulation or fluid balance of >2 liters in ICU patients.Fat-free mass loss (e.g., in patients in the ICU) relates to a worseprognosis for patients with chronic diseases. The association betweenfat-free mass at intensive care unit admission and 28-day mortality isone indicator. In the ICU population, known to have rapid fluid shifts,phase angle may be predictive of 28-day mortality The collectedsensorial data will enable a closed loop optimal control of patientnutritional intake which has been shown in patient faster convalescence.

At least some implementations of the systems, methods, apparatus, and/orcode instructions described herein improve the technology ofbioelectrical impedance analysis for measurement of body composition ofbody part(s) of a patient. The improvement arises, at least in part,from selection of certain electrodes on corresponding contact components(which may include an arrangement of three electrodes spaced apart andalong a long axis), which provides measurements of impedance ofcorresponding body portion(s). Electrodes may be selected according totheir respective addresses. A relatively small number of conductors maybe used when the segment of each body section is selected by theaddressable electrodes. The conductors (metallic layer or carbon basedlayer such as Graphene and/or inert metals such as gold and the like)may be mounted or deposited on a strip of flexible strip made of thinPCB material and/or Kapton (by Dupont) as an alternative amulticonductor cable can be used. In contrast, existing systems andmethods use one conductor for each electrode (for a point measurement ata certain location), which results in complexity of wiring, impracticalto measure impedance beyond a small number of locations due to the largenumber of conducting wires required, and/or interference between signalsarising from interference created by the large number of conducingwires.

Although fat-free mass (FFM) contains virtually all the water andconducting electrolytes in the body and FFM hydration is constant, thefundamental assumptions on which other systems and methods are based, isthat the body (i.e., limbs and trunk) are considered as a singleconductive cylinder and the relationship between the main crosssectional areas remains the same. This assumption is not relevant, forexample, for the elderly population, since with aging, the decrease inFFM and a redistribution of adipose tissue from the limbs to the trunkgive rise to narrower diameters for the conductive volumes (cylinders)of the limbs. To achieve improved accuracy and sensitivity inbio-impedance body composition measurement each cylinder (i.e., bodypart, for example, limbs and/or trunk) are measured independently (e.g.,segmental measurement) by at least some implementations of the systems,methods, apparatus, and/or code instructions described herein. The bodysegments reconstruction may include for an easier GUI color coding, forexample, blue for high water level and other color such as red fordehydrated body section.

At least some implementations of the systems, methods, apparatus, and/orcode instructions described herein improve the process of treating apatient based on bioelectrical impedance measurements. Water and/orelectrolyte content of body tissue are of clinical significance whentaking care of a patient and/or planning treatment of the patient. Theyindicative of, for example, dehydration, fat content, edema and otherpathological status indicators. Fat, cell boundaries and waterelectrolyte directly affect the electrical impedance of examined tissue.Hence the measurement of electrical conductance is increasingly beingused as an indication of patient health parameters. The improvementprovided is at least based on the ability to monitoring multipledifferent body parameters of the patient, using relatively fewconductors. The monitored data may be presented (e.g., in a GUI),analyzed for an indication of an alert, and/or used to predict futureclinical states of the patient and closed loop control of patient'snutrition.

At least some implementations of the systems, methods, apparatus, and/orcode instructions described herein may improve the technology ofperforming impedance measurement using a segmental approach. Thesegmental approach may refer to each impedance measurement beingperformed on a portion of the body, for example, a leg having a certainimpedance (denoted z) rather than the whole-body impedance (denoted Z).It is noted that using the segmental approach, a small change in theimpedance Δz is be much easier to sense since:

$\frac{\Delta z}{z}\operatorname{>>}\frac{\Delta z}{Z}$

Using standard approaches, segmental measurements require a large numberof leads and/or cables, which may cause discomfort to the patient,increase complexity, make the system cumbersome, and/or increase risk oferror in measurement.

The improvement provided by at least some implementations of thesystems, methods, apparatus, and/or code instructions described hereinis addressed by performing a segmental impedance measurement approachwithout the need of a large number of individual conductors and/orindividual electrodes as are required by existing systems and methods,and/or the capability of measuring the impedance of interior body organssuch as the lungs. The reduction in the number of conductors and/orelectrodes is due to the address architecture described herein, whereusing a small number of conductors—say 5 but less than 10 certainelectrodes (e.g., of certain contact components) may be selected, incontrast to existing methods in which each electrode is connected withits own dedicated pair of wires.

At least some implementations of the systems, methods, apparatus, and/orcode instructions described herein improve the technology ofbioelectrical impedance measurement and/or analysis, by enablingbioelectrical impedance measurement and/or analysis in conditions inwhich standard impedance measurement processes are inaccurate and/orcannot be used. In some cases, the optimal position for a patient onwhich impedance measurements are being performed is a full supineposition. However, due to clinical constraints the patient may not beplaced in the full supine position, for example, in patients with headinjury and/or intracranial pressure monitoring, and/or for patients forwhom the positioning of the electrodes is modified because of thepresence of other devices (e.g., intravenous cannulas and softrestraints). At least some implementations of the systems, methods,apparatus, and/or code instructions described herein enablingpositioning electrodes anywhere on the body, and/or the number ofelectrodes positioned on the body may be large, and/or selection ofdifferent electrodes enables performing bioimpedance measurements on anypart of the body.

Electrodes, when connected to contact components which are distinctphysical structures that are coupled to a common busbar, arepositionable anywhere on the body of the patient.

The data thus collected (i.e., impedance measurements of body segments,optionally per body segment as described herein) in conjunction withdata from other sensors, for example, respiration, resting energyexpenditure, pressure sensor, pulse sensor, sound sensor, and skinconductance sensor, and/or feed rate of nutrients and fluids, forexample, as described with reference to international patent applicationNo. IL 2017/051271 by the same inventors as the present application, maybe used via artificial intelligence (AI) models in a correlationanalysis between muscle mass (i.e., loss and/or gain) and nutrientconsumption/delivery/change by the patient in the ICU, with an analysisof the components in the feeding materials. The feeding may becorrelated with the data to provide an indication of how the feeding isaffecting the muscle status and/or otherwise health status of each bodysegment, optionally per body segment, since different body segments mayexperience different rates of muscle mass and/or health changes. Forexample, muscle mass may increase or decrease proportionally more inperipheral tissue in comparison to central tissue, or vice-versa. Musclemass and hydration status are considered as an important clinical healthand convalescence indicator and hence patient treatment should be tunedtowards improving the said muscle mass, the methodology just describedwill enable it. In comparison, known processes for adapting muscle massand hydration status are simple manual methods, for example, weightingthe patient using a scale, simple blood tests, and/or measuring thighcircumference.

The analysis may be indicative of the effect of body intake and specificfood contents on specific body section as analyzed by the impedance(and/or other) body sensors.

Optionally, muscle mass gain and/or loss is monitored (e.g.,continuously tracked), optionally per body segment, to allow dynamicfood and/or liquids enteral and/or parenteral modification by closedloop optimal control by applying the AI based model correlating the bodyintake with said muscle mass optionally per body segment. Instructionsmay be generated, optionally dynamically and/or in real time, forexecution by a feeding pump to change the feeding rate and/or food type,to reach a target, for example to adjust the feeding to prevent and/orreverse muscle loss and/or to help the patient gain muscle (e.g.,recover from muscle loss). For example, the amount of lipids,carbohydrates, proteins and/or fat in the administrated food iscontrolled according to estimated changes in the muscle mass. The amountof lipids, carbohydrates, proteins and/or fat may be selected based on acorrelation dataset that correlates between muscle mass changes and theamount of lipids, carbohydrates, proteins and/or fat which should beadministered to patient, for instance with certain physiologicalparameters, and/or demographic parameters. Different body segments mayrequire different proportions of lipids, carbohydrates, proteins and/orfat, for example, central tissues (e.g., belly) which have a higherproportion of fat may require different proportions of nutrients incomparison to peripheral tissues which may have relatively higherproportion of muscle. The amount may be selected per body segment usingthe correlation dataset that correlates between muscle mass changes andthe amount of lipids, carbohydrates, proteins, and/or fat per bodysegment. The amount per body segment may be aggregated (e.g., addedtogether, optionally using weights for different body segments) toobtain an overall amount/mixture of nutrition to administer to thepatient. The controller may generate instructions for automatic (and/ormanual and/or semi-automatic) delivery of the total nutrition (e.g., mixof nutrients and/or amount and/or rate of delivery and/or deliverypattern) to administer to the patient based on the nutrition determinedfor each segment, for example, by a feeding pump.

The modification may apply to the feed pump rate and/or foodspecifications, for example, as described with reference tointernational patent application No. IL 2017/051271.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not necessarily limited in itsapplication to the details of construction and the arrangement of thecomponents and/or methods set forth in the following description and/orillustrated in the drawings and/or the Examples. The invention iscapable of other embodiments or of being practiced or carried out invarious ways.

The present invention may be a system, a method, and/or a computerprogram product. The computer program product may include a computerreadable storage medium (or media) having computer readable programinstructions thereon for causing a processor to carry out aspects of thepresent invention.

The computer readable storage medium can be a tangible device that canretain and store instructions for use by an instruction executiondevice. The computer readable storage medium may be, for example, but isnot limited to, an electronic storage device, a magnetic storage device,an optical storage device, an electromagnetic storage device, asemiconductor storage device, or any suitable combination of theforegoing. A non-exhaustive list of more specific examples of thecomputer readable storage medium includes the following: a portablecomputer diskette, a hard disk, a random access memory (RAM), aread-only memory (ROM), an erasable programmable read-only memory (EPROMor Flash memory), a static random access memory (SRAM), a portablecompact disc read-only memory (CD-ROM), a digital versatile disk (DVD),a memory stick, a floppy disk, a mechanically encoded device such aspunch-cards or raised structures in a groove having instructionsrecorded thereon, and any suitable combination of the foregoing. Acomputer readable storage medium, as used herein, is not to be construedas being transitory signals per se, such as radio waves or other freelypropagating electromagnetic waves, electromagnetic waves propagatingthrough a waveguide or other transmission media (e.g., light pulsespassing through a fiber-optic cable), or electrical signals transmittedthrough a wire.

Computer readable program instructions described herein can bedownloaded to respective computing/processing devices from a computerreadable storage medium or to an external computer or external storagedevice via a network, for example, the Internet, a local area network, awide area network and/or a wireless network. The network may comprisecopper transmission cables, optical transmission fibers, wirelesstransmission, routers, firewalls, switches, gateway computers and/oredge servers. A network adapter card or network interface in eachcomputing/processing device receives computer readable programinstructions from the network and forwards the computer readable programinstructions for storage in a computer readable storage medium withinthe respective computing/processing device.

Computer readable program instructions for carrying out operations ofthe present invention may be assembler instructions,instruction-set-architecture (ISA) instructions, machine instructions,machine dependent instructions, microcode, firmware instructions,state-setting data, or either source code or object code written in anycombination of one or more programming languages, including an objectoriented programming language such as Smalltalk, C++ or the like, andconventional procedural programming languages, such as the “C”programming language or similar programming languages. The computerreadable program instructions may execute entirely on the user'scomputer, partly on the user's computer, as a stand-alone softwarepackage, partly on the user's computer and partly on a remote computeror entirely on the remote computer or server. In the latter scenario,the remote computer may be connected to the user's computer through anytype of network, including a local area network (LAN) or a wide areanetwork (WAN), or the connection may be made to an external computer(for example, through the Internet using an Internet Service Provider).In some embodiments, electronic circuitry including, for example,programmable logic circuitry, field-programmable gate arrays (FPGA), orprogrammable logic arrays (PLA) may execute the computer readableprogram instructions by utilizing state information of the computerreadable program instructions to personalize the electronic circuitry,in order to perform aspects of the present invention.

Aspects of the present invention are described herein with reference toflowchart illustrations and/or block diagrams of methods, apparatus(systems), and computer program products according to embodiments of theinvention. It will be understood that each block of the flowchartillustrations and/or block diagrams, and combinations of blocks in theflowchart illustrations and/or block diagrams, can be implemented bycomputer readable program instructions.

These computer readable program instructions may be provided to aprocessor of a general purpose computer, special purpose computer, orother programmable data processing apparatus to produce a machine, suchthat the instructions, which execute via the processor of the computeror other programmable data processing apparatus, create means forimplementing the functions/acts specified in the flowchart and/or blockdiagram block or blocks. These computer readable program instructionsmay also be stored in a computer readable storage medium that can directa computer, a programmable data processing apparatus, and/or otherdevices to function in a particular manner, such that the computerreadable storage medium having instructions stored therein comprises anarticle of manufacture including instructions which implement aspects ofthe function/act specified in the flowchart and/or block diagram blockor blocks.

The computer readable program instructions may also be loaded onto acomputer, other programmable data processing apparatus, or other deviceto cause a series of operational steps to be performed on the computer,other programmable apparatus or other device to produce a computerimplemented process, such that the instructions which execute on thecomputer, other programmable apparatus, or other device implement thefunctions/acts specified in the flowchart and/or block diagram block orblocks.

The flowchart and block diagrams in the Figures illustrate thearchitecture, functionality, and operation of possible implementationsof systems, methods, and computer program products according to variousembodiments of the present invention. In this regard, each block in theflowchart or block diagrams may represent a module, segment, or portionof instructions, which comprises one or more executable instructions forimplementing the specified logical function(s). In some alternativeimplementations, the functions noted in the block may occur out of theorder noted in the figures. For example, two blocks shown in successionmay, in fact, be executed substantially concurrently, or the blocks maysometimes be executed in the reverse order, depending upon thefunctionality involved. It will also be noted that each block of theblock diagrams and/or flowchart illustration, and combinations of blocksin the block diagrams and/or flowchart illustration, can be implementedby special purpose hardware-based systems that perform the specifiedfunctions or acts or carry out combinations of special purpose hardwareand computer instructions.

Reference is now made to FIG. 1, which is a schematic of a system 100for measuring body composition in one or more body portions of a patientby selectively activating electrodes (e.g., of electrode components) 118of a certain contact component (e.g., 114A) of multiple contactcomponents (e.g., 114A-B) connected by a multi conductor busbar (alsoreferred to herein as busbar), in accordance with some embodiments ofthe present invention, by another embodiment other sensors such aspressure, temperature, skin conductivity and pulse piezo sensors may beconnected to a busbar in addition to the impedance electrodes and/or asa separate entity. Reference is also made to FIG. 2, which is aflowchart of a computer implemented method for selectively activatingelectrodes of a certain contact component of multiple contact componentsconnected by a busbar, in accordance with some embodiments of thepresent invention. Electrodes 118 (optionally within an electrodecomponent including sub-components such as address decoder and/orswitches, as described herein) of contact components 114A-B, optionallythree per contact component, may be spaced apart and arranged along along axis (i.e., substantially straight ling) of the respective contactcomponent. One or more acts of the method described with reference toFIG. 2 may be implemented by components of system 100, as describedherein, for example, by a processor(s) 102 of a computing device 104executing code instructions 106A stored in a program store (e.g.,memory) 106.

Computing device 104 is in electrical communication with a controller108 (e.g., combined transmitter and receiver components, or separatetransmitter and receiver components 108) that generates instructions forselection of electrodes 118 on a certain contact component (e.g., 114A)from multiple contact components (e.g., 114A-B). Each set of electrodes118 on each contact component (e.g., 114A-B) are connected to a busbar112.

As used herein, the term electrodes (e.g., 118) may sometimes beinterchanged with the term electrode component, and/or may sometimesrefer to the electrode of the electrode component which includesadditional sub-components such as address decoder circuitry and/orswitches, or other bio sensors as described herein.

Each contact component may be made of, for example, flexible printedcircuit board and/or plastic and/or cloth, optionally flexible. Eachcontact component may include surface for placement against the bod ofthe patient, optionally against the skin. The surface may include anadhesive.

Optionally, one busbar 112 connects all of the electrodes on all of thecontact components. Alternatively, multiple busbars 112 are used, whereeach busbar 112 connects two or more contact components and coupledelectrodes. Each busbar 112 may be implemented, for example, multipleconduction lines (e.g., wires, strips of metal or other good conductingmaterials), optionally a single wire per dedicated task, for example, aline per each of: current, ground, power, voltage sensing, and/oraddressing, as described herein.

It is noted that there are multiple contact components. Two contactcomponents 114A-B are depicted as an example. Each contact component mayinclude the same or different number of electrodes 118 thereon.Optionally, each contact component includes three electrodes 118,optionally spaced apart and arranged along an axis (i.e., substantiallystraight line).

Controller 108 may include a transceiver for injection of electricalsignals to the electrodes assigned by the address code as currentelectrodes of the selected contact component, and receiving a signalfrom the electrodes of another contact component assigned by the addresscode as sensing electrodes, for example, the signal is injected into oneelectrode of one contact component which acts as a transmitter and ameasurement of the received signal by another electrode of anothercontact component is performed. Computing device 104 generatesinstructions for operating controller 108, and/or receives data fromcontroller 108, optionally via a device interface 110. Alternatively,computing device 104 and controller 108 are implemented as a singledevice and/or controller 108 is integrated within computing device 104,for example, as another hardware component and/or as code installed oncomputing device 104. When computing device 104 and controller 108 areintegrated, device interface 110 may be, for example, an internalsoftware interface.

Optionally, each biosensor is associated with a respective uniqueaddress. The biosensors are connected to the multi conductor busbarwhich is connected to at least some electrodes. The controller operatesthe biosensors and the electrodes by transmitting a certain uniqueaddress on the multi conductor busbar, as described herein.

Output from the other biosensor(s) connected to the multi conductorbusbar may be combined with the impedance measurement, for presentationand/or analysis.

The address instructions outputted by the controller may defineoperation of the corresponding electrode as a current carrier or voltagesensor.

Different components may be individually connected to the controllerforming mixed connections.

Optionally, a contact component with correspond electrodes is installedon an intra-body tube(s) 130. In another implementation, the contactcomponent is implemented as the intra-body tube(s) 130. Intra-bodytube(s) 130 enable obtaining measurements of composition of body partswithin the body, for example, of the lungs (e.g., to measure edema).Examples of intra-body tube(s) 130 include, an endo-tracheal tube (ETT),a naso-gastric (NG) tube, other feeding tube, a catheter, and/or othertubes designed for insertion into the body, for example, as describedwith reference to U.S. patent application Ser. No. 16/467,078, U.S.Publication No. 2010/0030133, U.S. patent application Ser. No.14/986,831, and U.S. patent application Ser. No. 16/000,922, by the sameinventors as the present application, incorporated herein by referencein their entirety.

Optionally, computing device 104 is implemented as hardware, forexample, circuitry, an assembly of hardware components, an integratedcircuit, and/or other architectures. Alternatively or additionally,computing device 104 may be implemented as, for example, a standaloneunit, a hardware component, a client terminal, a server, a computingcloud, a mobile device, a desktop computer, a thin client, a Smartphone,a Tablet computer, a laptop computer, a wearable computer, glassescomputer, and a watch computer. Computing device 104 may include locallystored software and/or hardware that perform one or more of the actsdescribed with reference to FIG. 2.

Processor(s) 102 of computing device 104 may be implemented, forexample, as a central processing unit(s) (CPU), a graphics processingunit(s) (GPU), field programmable gate array(s) (FPGA), digital signalprocessor(s) (DSP), and application specific integrated circuit(s)(ASIC). Processor(s) 102 may include one or more processors (homogenousor heterogeneous), which may be arranged for parallel processing, asclusters and/or as one or more multi core processing units.

As used herein, the term processor may sometimes be interchanged withthe term computing device.

Storage device (also known herein as a program store, e.g., a memory)106 stores code instructions implementable by processor(s) 102, forexample, a random access memory (RAM), read-only memory (ROM), and/or astorage device, for example, non-volatile memory, magnetic media,semiconductor memory devices, hard drive, removable storage, and opticalmedia (e.g., DVD, CD-ROM). Storage device 106 stores code instruction106A that execute one or more acts of the method described withreference to FIG. 2. Alternatively or additionally, one or more acts ofthe method described with reference to FIG. 2 are implemented inhardware.

Computing device 104 may include a data repository 116 for storing data,for example, a dataset that stores the impedance measurements obtainedfrom electrodes of different contact components for measurement of bodycomposition of the body portion of the patient, and/or the generatedmeasurements (e.g., body composition values), and/or an indication ofthe analyzed measurements (e.g., values of clinical parameters), and/ortrends in the measurements. Data repository 116 may be implemented as,for example, a memory, a local hard-drive, solid state memory device, aremovable storage unit, an optical disk, a storage device, and/or as aremote server and/or computing cloud (e.g., accessed via a networkconnection).

Computing device 104 includes and/or is in wired or wirelesscommunication with a user interface (and remote storage—processor suchas cloud) 118 that includes a mechanism for a user to enter data (e.g.,patient information) and/or view presented data (e.g., measurements ofcomposition for different body parts optionally in a GUI). Exemplaryuser interfaces 118 include, for example, one or more of, a touchscreen,a display, a keyboard, a mouse, and voice activated software usingspeakers and microphone. External devices communicating with computingdevice 104 may be used as user interfaces 118, for example, a smartphonerunning an application may establish communication (e.g., cellular,network, short range wireless) with computing device 104 using acommunication interface (e.g., network interface, cellular interface,short range wireless network interface).

Computing device 104 includes device interface 110 that provideselectrical communication with one or more controllers 108. Deviceinterface 110 may be implemented as, for example, a network interfacecard, a hardware interface card, a wireless interface, a physicalinterface for connecting to a cable, a virtual interface implemented insoftware, communication software providing higher layers of connectivity(e.g., application programming interface (API), software development kit(SDK), and/or other implementations.

Computing device 104 may include a network interface 120 for connectingto a network 122, for example, one or more of, a network interface card,a wireless interface to connect to a wireless network, a physicalinterface for connecting to a cable for network connectivity, a virtualinterface implemented in software, network communication softwareproviding higher layers of network connectivity, and/or otherimplementations.

Computing device 104 may communicate using network 122 (or anothercommunication channel, such as through a direct link (e.g., cable,wireless) and/or indirect link (e.g., via an intermediary computingdevice such as a server, and/or via a storage device) for example, withclient terminal(s) 124 and/or server(s) 126. For example, server(s) 126may receive the data collected from the electrodes 118 by the controller108, and compute the composition of the corresponding body portion(s) ofthe patient. Server(s) 126 may provide centralized computation servicesto multiple remote controllers 108 (and/or remote computing devices104). Server(s) 126 may analyze the data, for example to detect anindication of abnormality and/or predict a future abnormal composition,for example, by a machine learning model that is trained using dataobtained from multiple sample patients (e.g., via respective remotecomputing devices 104 and/or controller 108). Client terminal(s) 124 mayconnect to server(s) 126 and/or computing device 104 over network 122.For example, the image computed by server(s) 126 using data collected bythe computing device 104 is provided for presentation on a display ofclient terminal(s) 124. In another example, computing device 104 and/orserver(s) 126 may obtain additional data of the patient, for example,measurements made by other modalities, imaging results obtained fromother imaging modalities, and/or medical history data obtained from anelectronic medical record of the patient. The additional data may beused to analyze the measured composition body portion(s) of the patient,for example, to improve accuracy of detecting and/or predicting certainclinical states, such as edema.

Referring now back to FIG. 2, at 202, a setup of the system is providedand/or selected.

One or more different parameters of the system may be selected and/oradjusted, as follows:

Optionally, the number of contact components is selected. The number ofcontact components may be selected according to the number and/orlocation of body components being monitored and/or measured. Eachcontact component is positioned at the outer ends of the respective bodysegment being monitored and/or measured. Body segments may overlap oneanother, enabling the same contact component to be used for differentbody segments, reducing the number of electrodes used for monitoring.

The contact components are independent physical structures, which may beindependently positioned at different locations of the body. The contactcomponents are placed spaced apart. Positioning one contact component atone body part may be done without affecting the position of othercontact components at other body parts, since the contact components arenot physically connected, apart from a flexible busbar.

Each contact component includes multiple electrodes for contacting thebody of the patient, optionally the skin. Optionally, each contactcomponent includes three electrodes, optionally arranged along a longaxis of the contact component.

Optionally, each contact component is associated with a unique address.All electrodes of the contact component may be selected by the sameunique address. The electrodes of the contact component having theunique address may be independently operated (e.g., as a current source,current sink, voltage sensor and other biosensor) by instruction issuedby the controller to the unique address of the contact component.Alternatively, each electrode is associated with an electrode structurehaving its own unique address recognized by an address decoder. Eachelectrode may be independently operated by the controller providingoperating instructions to the unique address of the respectiveelectrode.

Optionally, each contact component includes a connector for connectingto the busbar, optionally reversibly, enabling detachment from thebusbar. Contact components may be added (i.e., connected) and removed(i.e., detached) from the busbar as desired, for example, to monitordifferent body segments on different patients. Alternatively, the busbaris pre-attached to the contact component in a manner where contactcomponents cannot be removed from the busbar without cutting theconnection.

Optionally, the number of busbars is selected. Optionally, at least onebusbar is connected to two or more electrodes (or electrode structures)of two or more contact components. Electrodes may be selected andoperated using the same common busbar via an address of the targetelectrode (and/or target contact component). Optionally, a single mainbusbar is used, where all contact components are connected to the mainbusbar. Alternatively, two or more busbars are used, for example, onebusbar connecting to contact components on the left side of the patient,and another busbar connecting to contact components on the right side ofthe patient.

Optionally, one or more intra-body probes, optionally tubes, forinsertion into the body of the patient are selected and/or designated.The intra-body tube is coupled and/or includes thereon one or morecontact components with multiple electrodes, or the electrodes andassociated circuity when the tube itself acts as the contact component(i.e., the term contact component may refer to the tube). The electrodesand/or contact component of the tube is connectable to one of thebusbars, and addressable by the controller, as described herein.Optionally, a busbar connects to the electrodes (i.e., the contactcomponent) of the tube and to one or more other contact componentspositioned externally t the body of the patient (e.g., on the skin).Exemplary contact components include: endotracheal tube (ETT), feedingtube, and naso-gastric (NG) tube, for example, as described withreference to U.S. patent application Ser. No. 16/467,078, U.S.Publication No. 2010/0030133, U.S. patent application Ser. No.14/986,831, and U.S. patent application Ser. No. 16/000,922, by the sameinventors as the present application, incorporated herein by referencein their entirety. Current and/or voltage may be measured between anelectrode on the tube and another electrode on a contact component onthe surface of the body of the patient, for example, impedancemeasurements performed by electrodes of the tube and a skin contactingcontact component is indicative of body composition of a lung, such asan amount of fluid in the lung and/or type of fluid in the lung.

Optionally some of the electrodes are connected to controller via theaddressing busbar while some are individually connected and assigned tothe controller via conductors i.e., a mixed interface connection ofelectrodes and other bio sensing elements.

Reference is now made to FIG. 3, which is a schematic depicting anexemplary architecture of an addressable electrode components 302 (alsoreferred to as electrode activation circuit), in accordance with someembodiments of the present invention. In an exemplary implementation,multiple electrode components 302 are part of a contact component 304,optionally three electrode components 302 along a long axis of contactcomponent 304, as descried herein.

Each electrode component 302 may include an address decodersub-component (e.g., circuitry) 302A for identifying the unique addressof the respective electrode component 302 transmitted on the multiconductor busbar 304, an electrode 302B which is operable to transmitcurrent, receive current, and/or measure voltage, and a switchsub-component 302C (e.g., circuitry) that connects the electrode 302B tothe relevant line of a multi conductor busbar 306 in response totriggering by the address decoder 302A recognizing the unique address onthe address line of the multi conductor busbar 306. Additional optionalsub-components of electrode component 302 include an amplifier foramplifying the measurement (e.g., voltage, current) by the electrode orother optional sensors 302B, and/or a sub-component that obtainsimplements instructions for operation of the electrode 302B receivedfrom the relevant line of the multi conductor busbar 306, for example,operating electrode 302B as the current source, current receiver, and/orvoltage sensor.

Multi conductor busbar 306, which is connected to the controller, mayinclude one or more of the following sub-components (e.g., as conductionlines) each for a dedicated task: Vcc line 306A for transmission ofpower to the electrode components 302, current injection line 306B fortransmission of a current to the electrode operating as current source,voltage sensing line 306C for receiving voltage measurements by anelectrode operating as a voltage sensor, ground 306D for acting as aglobal ground, and address line 306E for transmitting the unique addressfor selection and operation of a certain electrode structure. Additionaloptional lines include an instruction line for transmitting instructionsfor the operation mode of the electrode having the unique address (e.g.,current source, current sink, voltage sensor) and/or for a currentreception line for receiving current received by the electrode operatingas the current sink and lines connecting other sensors.

Reference is now made to FIG. 4, which is a schematic of an exemplaryimplementation of two contact component 404 coupled to the same multiconductor busbar 406, in accordance with some embodiments of the presentinvention. Optionally, multiple contact components and the busbar areintegrated into a single physical structure, optionally a long strip,for example, made of flexible printed circuit board, where each contactcomponent may be independently positioned at different parts of thebody. Each contact component 404 includes three electrode components402, each including an electrode 404B, one or more switches 402C, anaddress encoder 404A and other optional components as described herein.The busbar 406 includes a +5V DC line 406A, serial address line 406E,current line 406B, V1 line 406C, V2 line 406F, and ground line 406D.

As used herein, the term electrode component may sometimes beinterchanged with the term electrode, for example, when each electrodeis addressable.

Referring now back to FIG. 2, at 204, the contact components areattached to the body of the patient. Contact components may be attached,for example, by an adhesive surface which sticks to the skin of thepatient. Electrodes located beside the adhesive surfaces are placed incontact with the skin. In another example, contact components areattached via an outer and/or external connector, for example, wrapping abandage around the contact component and limb, or placing the contactcomponent between a pressure stocking and the leg of the patient. Tubesacting as contact components (or having contact components attachedthereon) may be inserted into the body of the patient.

Optionally, the busbar is connected to the contact components, beforeand/or after attaching the contact components to the body of thepatient. Alternatively, the busbar is pre-attached to the contactcomponents. The busbar may be flexible, enabling use of patients ofdifferent sizes.

Optionally, the electrodes (e.g., three) arranged along a long axis ofeach contact component are arranged and positioned on the patient alongan imaginary straight line drawn on the surface of the body of thepatient. For example, along an imaginary line running from the heel tothe wrist, the contact component is positioned along its long axisparallel to this imaging line, for example, on the ankle (e.g., in adirection from the feet to the head), and on the wrist (e.g., in adirection from the palm to the elbow.

The placement of the electrodes along the imaging line enables thecontroller, for example, to inject current and receive current using amiddle electrode of each contact component of a pair contact componentalong boundaries of a body segment, and to measure voltage using innerfacing electrodes of the pair of contact components. When a differentbody segment is monitored using one of the contact components alreadyused for another body segment, the current is again injected andreceived using the middle electrodes, and voltage is measured using theinner facing electrodes, where one of the currently inner facingelectrodes may have served as an outer acing electrode for measuring theother body segment. For example, placing contact components on thewrist, ankle, and chest, enable using three electrodes on three contactcomponents to measure the following segments: wrist-chest, chest-ankle,and wrist-ankle. The electrodes and contact component of the chestenable measuring the wrist-chest and chest-ankle segments as separatesegments that are in contact with one another.

By another option current is injected to the two extreme electrodeswrist to ankle and voltage is sensed from individual body segments.

Optionally, the human body may be considered as empirically composed ofthe following segments, each having a uniform electric conductivity:four limbs (left arm, right arm, left leg, right leg), and the trunk.Contact components may be positioned for measurement of impedance of oneor more of the segments.

Exemplary locations for placement of the contact component includes:wrist, ankle, chest, metacarpal line, metatarsal line, elbow, shoulder,armpit, knee, hip, neck, along midaxillary line, along midclavicularline, and the like.

Reference is now made to FIG. 5, which is a schematic depicting placedcontact components 502, which are independently addressable over acommon multi conductor busbar 504, for monitoring multiple body segmentsof a patient, in accordance with some embodiments of the presentinvention. Contact components (one is marked as 502 for clarity) areshown as placed on the wrist, shoulder, thigh, and ankle, as a notnecessarily limiting example. Each contact component 502 includes threeelectrodes 506 arranged along a long axis of the respective contactcomponent. A measurement console 508 acts as a controller for operatingthe electrodes 506 of the contact components 502 via addressableinstructions transmitted over the common busbar 504. Impedancemeasurements are analyzed and may be presented on a display 514, forexample as a Piccoli ellipse and/or depicting trend arrow superimposedon the Piccoli chart. Optionally, electrodes 510 are located within theesophagus, for example, positioned on a feeding tube. Electrodes 510 maybe used to measure impedance of internal segments, for example, thelungs, as described herein. Electrodes 510 may be connected to mainbusbar 504 or to another busbar 512. Electrodes 510 may be independentlyaddressable and/or operated by the controller, as described herein.

Reference is now made to FIG. 6, which is a schematic based on the setupdescribed with reference to FIG. 5, including an additional contactcomponent 602 with electrodes thereon positioned, for example, formeasuring of impedance for estimation of cardiac output (as denoted byarrow 604), in accordance with some embodiments of the present inventionand or lungs water content. Contact component 602 may be positioned inproximity to and/or above the heart of the patient, for example, at thebase of the neck as shown. Impedance measured using electrodes ofcontact component 602 and electrodes 510 located within the esophagusmay be analyzed for computation of cardiac output using bioimpedancecardiography in a non-invasive or minimally invasive manner, which mayperform better as a trend analysis of cardiac output in comparison tostandard approaches that measure absolute cardiac output (e.g., usingsensors placed within the heart and/or the circulatory system). Thesetup depicted is a four-terminal impedance monitoring (with oneterminal as address) setup.

Reference is now made to FIG. 7, which is a schematic based on the setupdescribed with reference to FIG. 6 (and FIG. 5), including additionalcontact components (one contact component 702 labelled for clarity)located on the left side of the patient's body, in addition to thecontact components positioned on the right side of the patient's body asin FIGS. 5 and 6, in accordance with some embodiments of the presentinvention. Positioning the electrodes on both sides of the patient'sbody and optionally inside the patient (e.g., in the esophagus) enablesmeasuring impedance in many different body segments defined by end pairsof selected contact components, on either side of the body and/or in themiddle of the body (e.g., between a contact component on the left sideand another contact component on the right side).

Reference is now made to FIG. 8, which is a schematic of an architecture802 in which each contact component (one contact component 810 labelledfor clarity) is connected to a main multi conductor busbar 804 via anindividual cable 806, in accordance with some embodiments of the presentinvention. A controller 808 transmits instructions to (and receivesmeasurements from) selected contact components via the address of therespective contact component over main busbar 804 and the individualcables 806. A single main busbar 804 may be used, or two or more mainbusbars, for example, one busbar connecting to cables of contactcomponents located on the left side of the body, and another busbarconnected to cables of contact components located on the right side ofthe body. The electrodes on the tube within the body (e.g., on thefeeding tube located within the esophagus) are connected to one of themain busbars. Contact components may be positioned on both sides of thebody as described with reference to FIG. 7, and as described herein,portion of the electrodes are connected to a busbar capable ofaddressing while others may be connected individually in a moreconventional way.

Reference is now made to FIG. 9, which is a schematic of an architecture902 in which each electrode (one electrode 910 labelled for clarity) isconnected to a main multi conductor busbar 904 via an individual cable906, in accordance with some embodiments of the present invention. Eachelectrode 910 may be associated with its own contact component, multipleelectrodes 910 may be associated with a single contact component (e.g.,two, three or more electrodes per contact component), or electrodes 910are directly placed on the patient without the contact component. Eachelectrode 910 may be part of an electrode component that includesaddressing circuitry for recognizing the unique address of therespective electrode, as described herein. A controller 908 transmitsinstructions to (and receives measurements from) selected electrodes viathe address of the respective electrode component over main busbar 904and the individual cables 906. Each electrode may be instructed tooperate in a selected operating mode (e.g., current source, currentsink, and/or voltage measurement sensor or other biosensor) according tothe instructions and associated address of the selected electrodetransmitted by the controller 908 over the main busbar 904. A singlemain busbar 904 may be used, or two or more main busbars, for example,one busbar connecting to cables of electrode components located on theleft side of the body, and another busbar connected to cables ofelectrode components located on the right side of the body. Theelectrodes on the tube within the body (e.g., on the feeding tubelocated within the esophagus) are connected to one of the main busbars.Electrode components may be positioned on both sides of the body. Forexample, for measuring an impedance Z1, electrode E1 is instructed tooperate as a voltage sensor and electrode E2 is instructed to operate asa current electrode. In another example, for measuring another impedanceZ2, electrode E1 is instructed to operate as a current electrode and E2is instructed to act as measurement electrode. It is noted that in orderto measure impedance, the electrode transmitting and/or receivingcurrent is located behind the electrode measuring voltage such that thecurrent, as it travels to and/or from the current electrode, passes bythe electrode sensing voltage. The contact component with three spacedapart electrodes arranged a long axis is designed to improve measurementof impedance by the relative placement of the current and voltageoperated electrodes, as described herein.

Reference is now made to FIG. 10, which is a schematic depicting anexemplary contact component 1002 placed in contact with a skin 1004 of apatient for measuring of impedance of a body segment including tissue1006, in accordance with some embodiments of the present invention.Contact component 1002 includes three electrode components 1008(sometimes also referred to as electrodes) arranged along a long axis ofthe contact component 1002. Contact component 1002 may include a supportstrip 1010 that connects to electrode components 1008, for example, as aflexible printed circuit board, plastic, cloth, textile and/or othermaterial. Each electrode component 1008 may include an address decoder1008A, electrode 1008B, and switch(es) 1008C, as described herein.

At 206, a body segment is selected for measurement of impedance thereof.Each body segment may be sequentially measured. Optionally, the mostinner/smallest segments are selected first, followed by larger segmentsthat include and/or overlap the inner/smaller segments. For example,first the wrist-chest segment, followed by the chest-ankle segment (orvice versa), followed by the wrist-ankle segment. Alternatively, thelarger segments are measured first, followed by the smaller segmentswhich may be located and/or overlap with the larger segment. Forexample, first the wrist-angle segment, followed by the wrist-chestand/or chest-ankle segment. Optionally, the selected segments arelocated within the body, for example, the lung and/or the heart (e.g.,for estimation cardiac output using impedance cardiography as describedherein). The internal segments may be measured using electrodespositioned within the body on probes (e.g., tubes), for example, on anasogastric tube positioned within the esophagus, as described herein.

Reference is now made to FIG. 11, which is a schematic depicting anexample of a measurement of a whole body segment 1102 and a measurementof a leg segment 1104, to help understand some embodiments of thepresent invention. Impedance of the whole body (denoted Z) may bemeasured, for example, by an electrode 1106 placed at a wrist andanother electrode 1108 placed at an ankle. Impedance of the leg segment(denoted z) may be measured, for example, by an electrode 1110 placed atan upper part of the leg (e.g., thigh, hip) and another electrode 1112placed at the ankle of the leg. The impedance measured for a bodysegment (e.g., for the leg as in 1104) may be 10 time more sensitivethan impedance measured for the whole body (e.g., as in 1102). It isnoted that values obtained using the setup depicted in 1102 correspondto BIVA type impedance measurements.

Reference is now made to FIG. 12, which includes Picccoli diagrams for awhole body measurement 1202 and for a body segment 1204, to helpunderstand improved accuracy of impedance measured for the body segmentin comparison to the whole body. Piccoli diagram 1202 for the wholebody, which may be using the whole body segment measurement setup 1102of FIG. 11, depicts angular change due to local impedance change denotedα_(A). Piccoli diagram 1204 for the body segment, which may be using theleg body segment measurement setup 1104 of FIG. 11, depicts angularchange due to local impedance change denoted α_(B). The increase insensitivity of segmental measurement over whole body measurement isdenoted as α_(A)>>α_(B).

At 208, the controller selects and activates and/or operates a pair ofcontact components (and/or electrodes thereof) connected by a commonmulti conductor busbar. Electrodes on each of the contact components maybe selected and activated and/or operated. Selection and activationand/or operation may be sequential, for example, first one member of thepair, followed by the second member of the pair.

Exemplary operation modes may include: current source, current sink,voltage sensor and other biosensor.

The controller generates and transmits instructions for activationand/or operation of the certain contact component (and/or electrodethereof) by transmitting the unique address of the certain contactcomponent (and/or electrode thereof) on the busbar, for example, on anaddress line component of the busbar. Instructions for operation in acertain operation mode may be transmitted in association with the uniqueaddress, for example, on another line component of the busbar. Circuitryof the contact component corresponding to the unique address implementthe instructions (e.g., to operate in the designated operation mode).

Other contact components (and/or electrode components) may listen to thebusbar for their address and ignore the instructions when the address isnot assigned to them. Addressing may be defined, for example, by a setof sequential and/or parallel signal bits transmitted over the busbar(e.g., over the dedicated address line component of the busbar).

At 210, one or more impedance measurements of the selected body segmentare obtained from the pair of contact components (i.e., from electrodesthereof). Optionally, voltage and current measurements are obtained fromthe pair of contact components. The impedance measurement is computedfrom the obtained voltage and current measurement.

The applied current may be an alternating current (AC) and/or directcurrent (DC).

Optionally, as another embodiment, the electrodes and/or sensors may bemounted inside an inner wall of a sleeve (e.g., made from textile,plastic, and/or other materials or material combination) havingoptionally a double wall. The sleeve may be applied on a patient's bodypart. In use, when the sleeve is placed on the body, the electrodescontact the body of the patient, optionally the skin. Electrodecomponents are connected via the busbar and optional cable to thecontroller, as described herein. The lumen formed by the double wall maybe inflated. The inflated lumen may increase probability and/orguarantee substantially uniform equal pressure on all electrodes formore uniform measurements. Inflation may be controlled by the controllervia a pump connected to an inflation tube of the sleeve.

Optionally multiple sensor strips may be applied on the patient's bodypart by adhesive enabling, for example, in both embodiments 3D impedancemapping of the body part.

Reference is now made to FIG. 18, which includes a schematic 1800A of across section of a foot of a patient an inflatable sleeve 1802 withelectrodes 1804 located within the inner wall of the sleeve, inaccordance with some embodiments of the present invention. Sleeve 1802includes a busbar 1806 and/or inflation tube 1808 which connect to acontroller, as described herein. FIG. 18 also includes a schematic 1800Bof a cross section of a foot with electrodes 1850 on conductor strips1852 (e.g., spaced apart electrodes on contact components), inaccordance with some embodiments of the present invention. There may bemultiple conductor strips 1852 connected to a single main busbar 1854.Each strip 1852 of electrodes 1850 may be independently positioned onthe leg by an adhesive. It is noted that schematics 1800A and 1800B maybe combined, where strips of electrodes are positioned within theinflatable sleeve, for example, using Velcro, straps, and/or otherconnecting materials.

Optionally, multiple impedance measurements are obtained, optionally atdifferent current frequencies—multi frequency, for example, in the rangeof about 10 Hz, 100 Hz 1000 Hertz (Hz) to 100 kiloHertz (kHz), or 1 kHzto 1000 kHz, optionally using a center frequency of 50 kHz. Exemplaryfrequencies include: 1 kHz, 5 kHz, 50 kHz, 250 kHz, 500 kHz, and 1000kHz. Frequencies may be in increments of, for example, 1 kHz, 10 kHz, orother values, or continuous measurements with continuous variation offrequency. A 3D map may be created and presented using a linear graduatemeasurement of the different frequencies, as described herein.

Current (e.g., AC and/or DC) may be sinusoidal shaped or other pattern.

Current amplitude may be, for example, about 10, 100, or 200, or 400, or1000 microamperes, or other values.

An exemplary current used for the estimation of FFM is an alternatingsinusoidal electric current of 400 μA at a single operating frequency of50 kHz.

Optionally, the computed impedance is a complex value. The real part(denoted R) and the imaginary part (denoted X) may be computed.

The impedance is indicative of an estimation of body composition of theselected body segment.

At 212, one or more features described with reference to 206-210 areiterated. Optionally, the iterations are for obtaining impedancemeasurements of different body segments, and/or for monitoring impedancevalues of the same body segments(s) over time by obtaining multipleimpedance values over a time interval.

Optionally, the controller iteratively switches between different pairsof contact components of different body segments to obtain impedancemeasurements over a time interval for monitoring each of the bodysegments. For example, one or more impedance measurements are obtainedfor one body segment, then another set of impedance measurements isobtained for another body segment, where the cycle of measurements forthe first and the second body segment are iterated over time.

Optionally, smaller segments are measured first. Larger segments, whichinclude two or more smaller segments therein, may be measured later.Alternatively, first larger segments are measured, and then two or moresmaller segments located within the larger segments are measured.

Alternatively, a single segment is selected for monitoring, for example,for monitoring hydration level of a lower leg. Contact components ofother segments may be electrically decoupled or otherwise not activatedby the controller.

Optionally, the controller iteratively selects another (e.g., second)pair of contact components from the set of contact components connectedby the common multi conductor busbar. The contact component of the firstpair of contact components may be positioned between the second pair ofcontact component. For example, the first pair of contact components arelocated on the wrist and along the midaxillary line, and the second pairof contact components are located on the wrist (i.e., the same wristcomponent as in the first pair) and on the ankle. Alternatively, thefirst and second pairs are switched. The first and second pair ofcontact components are connected to the same common multi conductorbusbar.

Optionally, when contact component of the first pair are positionedbetween the second pair of contact component, the electrodes of thefirst pair are non-selected and not activated during the impedancemeasurement performed for the respective body segment located betweenthe second pair of contact components. One of the second pair of contactcomponents may be selected from the first pair of contact components.For example, when the first pair measures impedance of the body segmentbetween the wrist and chest, and the second pair measures impedance ofthe body segment between the wrist and ankle, the contact componentspositioned on the chest (i.e., between the wrist and ankle) is notselected and not activated during impedance measurements of the bodysegment between the wrist and ankle. The wrist contact components may beused for impedance measurements of both the wrist-ankle and wrist-chestbody segments.

Optionally, for the architecture of the contact component includingthree (or more) electrodes optionally aligned along a long axis of thecontact component, where all electrodes of the multiple contactcomponents are optionally aligned along an imaginary straight line drawnon the skin of the patient (it is noted that the line may be straightalong the skin, but curve according to surface features of the skin),the controller may inject and receive current using a middle electrodeof each contact component of the first pair and second pair of contactcomponents. Voltage may be measured using inner facing electrodes of thefirst pair and second pair of contact components. For example, formeasuring the wrist-chest and chest-ankle body segments, the middleelectrode of the chest contact component is used for current. Theelectrode of the chest contact component closer to the wrist is used forthe wrist-chest segment, and the other electrode of the chest contactcomponent closer to the angle is used for the chest-ankle segment. Forthe wrist-ankle segment, the chest contact component is unused.

Reference is now made to FIG. 13, which is a schematic depicting aprocess of selective activation of electrodes of multiple contactcomponents for sensing multiple body segments, in accordance with someembodiments of the present invention. The process is executed byinstructions transmitted by a controller over a busbar, as describedherein. Contact components 1304, 1306, 1308, which are placed againstbody of patient 1310, each include three respective electrodes 1304A-C,1306A-C, 1308A-C arranged along a longitudinal line.

Schematic 1302A depicts the process of measuring impedance of the bodysegment (denoted A) between contact components 1304 and 1306. Middleelectrode 1304B is operated as a current injector, and middle electrode1306B is operated as a current collector, while voltage is measuredbetween inner facing electrodes 1304C and 1306A.

Schematic 1302B depicts the process of measuring impedance of the bodysegment (denoted B) between contact components 1304 and 1308. Middleelectrode 1306B is operated as a current injector, and middle electrode1308B is operated as a current collector, while voltage is measuredbetween inner facing electrodes 1306C and 1308A.

Schematic 1302C depicts the process of measuring impedance of the bodysegment (denoted C) between contact components 1304 and 1308. It isnoted that body segment C includes both body segments A and B. Outerelectrode 1304A is operated as a current injector, and middle electrode1304 is operated for voltage measurement. Alternatively, middleelectrode 1304B is operated as a current injector, and middle electrode1308B is operated as a current collector, while voltage is measuredbetween inner facing electrodes 1304C and L08A. In either case, theprinciple of operation is to have two current injecting electrodes andbetween the two current injecting electrodes there are two voltagesensing electrodes, which is the desired 4 electrodes approach toimpedance sensing.

At 214, the obtained impedance data is analyzed. The impedance data maybe analyzed over small time intervals (e.g., single measurement of setof closely spaced measurements such as at different frequencies, forexample, less than about 1 second, or 10 seconds, or 1 minute) such asto obtain a real time value, analyzed over large time intervals (e.g.,about 10, 15, 30, 60, 120 minutes, 6, 12, 24, 48, 72 hours, 1 week, orother values) such as to compute trends.

Optionally, body composition is estimated for each body segmentaccording to impedance values obtained for the respective body segment.Exemplary body composition include fat content, edema, water content,electrolyte content, and pathological status.

Alternatively or additionally, the impedance measurements of one or morebody segments are analyzed for determining whether a current target hasbeen reached, for example, whether the body composition of therespective segments reached a clinically significant target. Optionally,an alert is generated when the target has been reached, for example, apop-up notification on a display, and/or a text message is sent to amobile device of an on call physician.

Alternatively or additionally, the impedance measurements of one or morebody segments are analyzed for making a prediction, for example, whenthe body composition of the respective segments reaches a clinicallysignificant target. An alert indication of the prediction may begenerated and provided, for example, patient is predicted to reachtarget in the next 15 minutes. The prediction may be computed, forexample, using a trend analysis (e.g., least square fit of a trend lineto predict when the trend line will cross the threshold) and/or feedingthe data into a machine learning model trained on data and an indicationof a result, for example, a neural network.

Exemplary clinically significant targets include dehydration, and fluidoverload.

Impedance values may be analyzed for computing the following exemplaryhealth parameters:

-   -   ECW—extra cellular water which form the main conduction body at        low frequencies.    -   ICW—Intra cellular water conducting at high frequency.    -   TBW—Total body water, indication of the body hydration status.    -   FFM—Fat free mass.    -   % body fat. Indication of obesity status of the patient.

Other parameters such as lungs water content may be calculated as partof the general patient status.

Reference is now made to FIG. 14, which includes some exemplary BISequations, in accordance with some embodiments of the present invention.

Reference is now made to FIG. 15, which includes some exemplaryequations for computing exemplary health parameters, in accordance withsome embodiments of the present invention. The exemplary parameters maybe computed for each of the monitored body segments.

At 216, the data and/or analyzed data is provided. The data and/oranalyzed data may be presented on a display, for example, within agraphical user interface (GUI), stored in a memory (such as in theelectronic health record of the patient, and/or locally on the computingdevice), and/or provided to another process for further processing(e.g., locally executed and/or executed on a remote server and/orcloud).

Optionally, the body composition for the respective body segments ispresented within a GUI. The GUI may be dynamically updated in real time,as new impedance values are obtained and/or analyzed, for example, asdescribed with reference to 220.

Optionally, the body composition of the respective body segments arepresented (e.g., within the GUI) corresponding to a body map thatdepicts locations of the respective body segments.

Alternatively or additionally, the estimated amount of body compositionof the respective segments are presented (e.g., within the GUI) as anindication along a range of different body compositions, for example,optionally color coded. For example, blue for body segments having ahigh water level and other color such as red for dehydrated bodysegments.

Optionally, a 3D map is computed and optionally presented usingimpedance measurements obtained at multiple different frequencies foreach body segment. The 3D map may be presented using a linear gradientmeasurement based on the different frequencies.

Optionally, a trend line is computed and presented within the GUI. Atarget body composition may be presented with respect to the trend line.The visual presentation may help the user visualize when the bodycomposition is predicted to reach the target according to the trendline.

Reference is now made to FIG. 16, which is a schematic depictingexemplary presentations 1602 1604 based on analyzed impedancemeasurements of body segments, in accordance with some embodiments ofthe present invention. Presentations 1602 1604 may be presented, forexample, within a GUI on a display of a client terminal, as describedherein.

Presentation 1602 is a graph computed based on the Cole-Cole complexplan approach, where the measured impedance is mapped on an R-X complexplane. In the presented example of presentation 1602, the 50 kHzimpedance (which may be considered a cardinal parameter) is mapped and atrend extrapolation 1606 is computed and presented. Portions of the R-Xplane corresponding to clinically significant states (e.g., pathologicalstates) may be defined. For example, region 1608 located in the upperright section of the R-X plane denotes dehydration. An alert 1610denoting that the patient is dehydrated may be presented, for example,when the impedance measurements are located within dehydration region1608 and/or when the trend indicates that the patient is not yetdehydrated but predicted to become dehydrated at a future time. Anindication of a phase angle 1612 may be computed and presented. Thephase angle and/or amplitude may be an important clinical factor, forexample Piccoli suggested that the normal parameter value should becaptive inside an ellipse and departure from the ellipse may beconsidered pathological.

Presentation 1604 is a table summarizing values of some clinicalparameters (in a column 1614) for different body segments (in a row1616), such as arm (e.g., left and/or right), torso, leg (e.g., leftand/or right), and total (i.e., whole body). Each cell (e.g., 1618) inthe table presents an indication of the corresponding clinical parameterfor the corresponding body segment, for example, as a dot within a barrange. Other indications may be used, for example, numerical values,color coding, and category indications. One or more important parametersmay be presented in a box 1620, for example, parameters selected by theuser, parameters which are predefined as important, and/or parametershaving abnormal clinically significant values.

Reference is now made to FIG. 17, which is a schematic of an exemplarypresentation of impedance data for multiple body segments, in accordancewith some embodiments of the present invention. The presentation may bepresented on a display as a GUI, as described herein. The presentationmay include a body map 1702, such as a schematic/image of a body of apatient. Monitored body segments may be presented with respect to bodymap 1702, for example, marked on body map 1702 and/or as an overlay onbody map 1702, for example, as zigzag lines 1706. As shown, eight bodysegments are being monitored, denoted Z1, Z2, Z3, Z4, Z5, Z6, Z7, andZ8. Location of contact components (including electrodes) may be withrespect to body map 1702, for example, marked on body map 1702 and/or asan overlay on body map 1702, for example, as a dark box 1704. The bodysegments right wrist-right shoulder Z1, right shoulder-right hip Z2,right hip-right ankle Z3, left ankle-left hip Z4, left hip-left shoulderZ5, left shoulder-left wrist Z6, left shoulder-right hip Z7, rightshoulder-left hip Z8, may be monitored using 8 contact components (e.g.,located on the left wrist, right wrist, left shoulder, right shoulder,left hip, right hip, left ankle, and right ankle, or in proximity to thestated locations). An indication of the amount of one or more monitoredclinical parameter (computed based on an analysis of the impedancevalues, as described herein) may be presented for one or more bodysegments, for example, for each segment, for user selected segments,and/or for segments having abnormal values. The indication may be, forexample, presented as an arrow with respect to a range, optionally colorcoded, denoting normal and abnormal values. For example, as shown,result icon 1708A denotes a normal value of fluid for body segment Z1(e.g., arrow pointing to green colored zone of the values bar), resulticon 1708B denotes a normal value of fluid for body segment Z6 (e.g.,arrow pointing to green colored zone of the values bar), result icon1708C denotes a high water accumulation amount for body segment Z3(e.g., arrow pointing to blue colored zone of the values bar), andresult icon 1708D denotes a dehydration state for body segment Z4 (e.g.,arrow pointing to red colored zone of the values bar).

At 218, the patient may be diagnosed and/or treated and/or treatment maybe planned according to the presented data, for example, according tothe estimated body composition, for example, medications may beprescribed, fluids may be administered, imaging may be performed (e.g.,chest xray, CT, MRI, such as when lung fluid is detected), a cathetermay be inserted, tubes may be removed, surgical procedures may beperformed, and/or nothing is done at the moment.

The diagnosis and/or treatment and/or treatment recommendation may bemanually determined and/or automatically determined by code, forexample, by a trained machine learning model trained on impedance valuesand corresponding actions taken by expert physicians.

The analysis and/or diagnosis and/or treatment recommendation may beperformed remotely, for example by code residing in a cloud and/orserver, in response to locally collected impedance data. The centralprocessing of the data enables using data collected from differentpatients at different medical sites, increasing diversity of the data(e.g., different patient demographics, different clinical protocolsfollowed, different levels of physician training, different availabletreatments).

At 220, one or more features described with reference to 206-218 areiterated, for example, for dynamic updating of the GUI, alerts,predictions, and/or indication of diagnosis.

Reference is now made to FIG. 19, which is a flowchart of an exemplaryprocess of monitoring a heart of a subject using electrocardiogram (ECG)measurements and/or monitoring impedance-related parameters and/ortreating the subject based on the ECG measurements and/or theimpedance-related parameters, where the ECG and impedance measurementsare obtained from electrodes on a feeding tube positioned in theesophagus, in accordance with some embodiments of the present invention.The features of the methods described with reference to FIG. 19 may beimplemented by components of system 100 described with reference to FIG.1, and/or features of implementations described with reference to FIGS.2-18. For example, by a controller implemented as computing device 104that includes memory 106 storing code 106A that when executed byprocessor(s) 102, causes processor(s) 102 to execute features of themethod described with reference to FIG. 19.

At 1902, the feeding tube is inserted into, and/or located at, a distalend of an esophagus of the subject. The feeding tube is positioned inthe esophagus for enteral feeding of the subject.

One or more electrodes are located on the distal and of the feedingtube. When the tube is in the esophagus, in use for feeding, theelectrode(s) are located at the distal end of the esophagus.

There may be multiple spaced apart electrodes on the feeding tube.

The feeding tube and/or electrodes may be as described herein.

At 1904, additional electrodes may be positioned on the body of thepatient. The additional electrodes may be extracorporeal electrodeslocated externally to the body of the subject, and contacting the bodyof the subject.

Optionally, the additional electrodes are standard ECG electrodesapplied to the skin surface of the chest of the subject in a standardECG measurement arrangement. Alternatively or additionally, theadditional electrodes are contact components, used for measuringimpedance, as described herein. The contact components described hereinmay be used to obtain ECG measurements at different locations on thebody, as described herein.

One or more of the following features described with reference to1906-1924 are performed while the feeding tube is in located in theesophagus and feeding material is delivered to the patient via thefeeding tube. This allows continuous and/or real time monitoring and/ortreatment of the heart of the subject (and/or other features asdescribed herein) while the patient is being fed.

At 1906, voltage is measured at one or more electrodes of the feedingtube. Voltage may be measured at one or more other electrodes, such asthe extracorporeal electrodes, contact components, standard ECGelectrodes, and the like.

When voltage is measured at the electrodes, no current is beingadministered via the electrodes (e.g., zero input current, or nearzero). When no external current is present, the potential measured bythe electrode(s) on the feeding tube in contact with the inner tissue ofthe esophagus is an indication of internal potential source originatingfrom inside the observed tissue (excluding noise), which includeselectrical signals generated by the heart.

Optionally, at least one electrode on the feeding tube is continuouslyin contact with inner tissue of the esophagus. The electrode(s) may belocated on the feeding tube at a location corresponding to the loweresophageal sphincter (LES) (e.g., when the feeding tube is correctlypositioned) so that the electrode is in continuous contact with the LES.In another example, one or more electrodes may be located on a balloon(and/or other expandable element) located on the feeding tube. Theballoon may be expanded to contact the electrode(s) with the innertissue of the esophagus.

Optionally, one or more electrodes on the feeding tube are not incontact with the inner tissue of the esophagus. For example, locatedalong the length of the feeding tube above the LES, where the diameterof the feeding tube is significantly smaller than the diameter of theesophagus. Such electrodes may be used for monitoring reflux within theesophagus by measuring impedance.

Optionally, voltage is measured continuously, while one or more featuresdescribed with reference to 1906-1914 are iterated. Alternatively,voltage is measured at spaced apart time intervals, and/or at certaintime intervals, for obtaining ECG measurements and/or impedancemeasurements. ECG sample times may be defined, for example, atpreselected time intervals, for example, about every 0.5 seconds, or 1second, or 5 seconds, or 10 seconds, or 30 seconds, or 1 minute, orother time intervals. ECG may be sampled over a time intervalsufficiently long to include one or more cardiac cycles, for example, atleast about 1 second, or 5 seconds, or 10 seconds, or 30 seconds, or1-30 seconds, or 5-20 seconds, or other time intervals.

At 1908, a current, optionally, an alternating current, is appliedbetween one or more electrodes of the feeding tube and one or more otherelectrodes. The applied current establishes a current channel betweenthe electrode(s) of the feeding tube and the other electrode(s). Thealternating current may be applied at a selected frequency. Multiple ACcurrents may be applied, each at a respective frequency, for example,simultaneously and/or sequentially.

Optionally, the current is applied at the same electrode(s) where thevoltage is being measured.

Optionally, the other electrode(s) may be other electrodes on thefeeding tube, i.e., so that the current channel is established between apair (or more) of electrode on the feeding tube. Alternatively oradditionally, the other electrode(s) may be the extracorporealelectrodes and/or electrodes of the contact components.

Optionally, a non-cardiac current channel is established that avoidsand/or reduces the amount of current flowing through the heart of thesubject, for example, as described with reference to U.S. ApplicationPublication No. 2019-0313970, by the same inventors of the presentapplication.

At 1910, one or more impedance measurements are obtained from theelectrode(s) of the feeding tube and/or from the other electrode(s). Theimpedance measurements are computed based on the applied current and themeasured voltage.

At 1912, one or more impedance-related parameter may be computed basedon the impedance measurements. Exemplary impedance related-parametersinclude:

-   -   An indication of location of the tube within the esophagus, for        example, relative to the lower esophageal sphincter (LES). For        example, to detect when the tube moves out of the correct        position. Additional details of exemplary systems and/or methods        for monitoring the position of a tube based on impedance        measurements computed based on electrode(s) located on a tube        positioned within the esophagus may be found with reference to        U.S. Pat. No. 9,713,579, by the same inventors of the present        application.    -   An estimate of a level of fluid within the digestive system. The        enteral feeding (e.g., rate, mixture, amount of water, amount of        protein) may be automatically adjusted according to the        estimated fluid level, for example, to prevent reflux.        Additional details of exemplary systems and/or methods for        estimating fluid levels based on impedance measurements computed        based on electrode(s) located on a tube positioned within the        esophagus may be found with reference to International Patent        Application No. IL2015/051156, by the same inventors of the        present application.    -   An indication of body composition of a body segment located        between the electrodes via which the current channel is        established, for example, lung fluid, and/or other body        composition indications as described herein.    -   An indication of reflux, i.e., detecting a gastric reflux event.        For example, to stop enteral feeding. Additional details of        exemplary systems and/or methods for detecting reflux event        based on impedance measurements computed based on electrode(s)        located on a tube positioned within the esophagus may be found        with reference to International Patent Application No.        IL2017/050634, by the same inventors of the present application.    -   An indication of breathing motion and/or motion of the diaphragm        of the subject, optionally when the subject is being        mechanically ventilated by a mechanical ventilator.    -   Estimate functionality of lung(s) according to a correlation        between impedance values and lung function, and/or a correlation        between lung fluid and lung function, for example, as described        with reference to U.S. Application Publication No. 2019-0313970,        by the same inventors of the present application. As lung fluid        increases, the functionality of the lungs decreases.        Functionality of the lungs may be for example, in terms of        oxygen and carbon dioxide exchange, and/or air volume capacity        of the lungs. Oxygen and carbon dioxide exchange is decreased        due to the amount of tissue available to perform the exchange,        since fluid filled tissue (i.e., pulmonary edema) cannot perform        such exchange. Alternatively or additionally, the lung may be        compressed from external fluid (e.g. pulmonary effusion) which        reduces the volume of air capacity of the lung, reducing lung        efficiency. The estimate of lung fluid (e.g., amount of fluid,        change relative to a baseline) may be correlated to lung        function, for example, according to a graph and/or function,        which may be empirically measured and/or computed based on        mathematical models. The estimated lung function may be computed        as a change relative an initial baseline (e.g., 100%). For        example, a certain increase in lung fluid may correspond to a        10% decrease in lung function. In another example, a 15%        decrease in impedance may correspond to a 5% decrease in lung        function.

At 1914, the application of the current (e.g., the alternating current),is terminated.

At 1916, an ECG measurement is obtained based on the voltage measured atleast at one or more electrode(s) of the feeding tube. The ECGmeasurements is obtained while no current is being applied to theelectrode(s) of the feeding tube.

Optionally, the ECG measurement is obtained from the electrode(s)contacting the inner surface of the esophagus, for example, theelectrode(s) positioned on the feeding tube for contacting the LESand/or electrode(s) positioned on expandable elements (e.g., balloon) onthe feeding tube when the expandable elements are expanded.

Optionally, multiple ECG measurements are obtained. ECG measurements maybe obtained from each one of multiple spaced apart electrodes located onthe distal end portion of the feeding tube. Each respective ECGmeasurement obtained at a respective electrode of the feeding tubedenotes a different orientation relative to the heart of the subject.For example, one or more electrode(s) may be located on the feedingtube, so that when the feeding tube is in a predefined location (e.g.,relative to the LES), the electrode(s) is in closest proximity to thesinoatrial node. Other electrodes may be positioned relatively higherand/or lower to capture ECG signals in proximity to other locations, forexample, tricuspid valve right atrium, right ventricle, septum, mitralvalve, left atrium, left ventricle, and/or other portions of theconduction system of the heart.

ECG measurements may be obtained after voltage(s) measured when nocurrent is being applied undergo signal processing, for example,electronic filtering for removal of noise and/or unwanted electricalinteractions. Filters may be tuned for detecting ECG, for example,matched filters tuned for ECG type wave forms, time domain moving windowcorrelation for emphasizing the true ECG wave form while suppressingother spurious sources and/or noise. Since the ECG signals are of lowfrequency type (vis a vis capability of electronic circuits),sophisticated digital matched filtering may be applied.

At 1918, the measured impedance-related parameter and/or the ECGmeasurement may be provided, for example, presented on a display, storedin a memory, forwarded to a remote computing device (e.g., server,mobile device, smartphone), and/or provided to another process forfurther processing, for example, for analysis as described herein.

At 1920, the ECG measurements may be analyzed to determine an indicationof cardiac abnormality, for example, arterial and/or ventricle pacingproblems, cardiac arrest, and arrhythmias. The analysis may beautomatically performed (e.g., by the controller and/or other computingdevice) and/or manually performed by a user (e.g., based on thepresentation of the ECG on a display). The automatic analysis may beperformed, for example, based on a set of rules, a trained classifiertrained on a training dataset of ECG samples and labelled with a groundtruth cardiac abnormality, and/or based on the T and/or QST portions.

Optionally, each one of multiple ECG measurements obtained fromrespective electrodes on the feeding tube may be analyzed individually.Alternatively, the multiple ECG measurements obtained from respectiveelectrodes on the feeding tube may be analyzed as a combination, forexample, as a group, to obtain an overlap state of the heart based onthe ECGs obtained at different views.

The analysis of the ECG measurements obtained from electrode(s) on thefeeding tube may include and/or be in combination with ECG measurementsobtained from standard ECG electrodes applied to the chest of thesubject.

Optionally, the ECG measurements are analyzed in combination with one ormore impedance-related parameters. Optionally, The ECG measurements areanalyzed with the impedance-related parameters indicative of bodycomposition, for example, indicative of lung fluid. Alternatively oradditionally, the ECG measurements are analyzed with theimpedance-related parameters indicative of breathing and/or diaphragmmotion, for example, indicative of the patient's breathing pattern.Alternatively or additionally, the ECG measurements are analyzed withthe impedance-related parameters indicative of reflux, for example, todistinguish chest pain as being due to a cardiac condition (e.g., heartattack) versus reflux.

Optionally, the analysis of the ECG measurements, optionally incombination with one or more impedance-related parameters, is performedto determine likelihood of an abnormal cardiac condition. For example,tachycardia and/or conduction problems in the heart.

The analysis of the ECG measurements may be performed, for example,based on a set of rules, based on a mapping function, and/or based on amachine learning (ML) model such as a statistical classifier (e.g.,neural network, regression function, support vector machine, and thelike) trained on a training dataset of records of sample subjects thatinclude ECG measurements obtained from electrodes on a feeding tubepositioned in the esophagus of the respective subject and correspondingground truth cardiac conditions (e.g., determined by qualifiedphysicians).

Optionally, the analysis is performed based on a combination of ECGmeasurements and body composition (i.e., impedance-relatedparameter(s)), for example, indicating amount of lung fluid in lung(s)of the subject Likelihood of the cardiac abnormality may be determinedbased on the combination of ECG and body composition. For example, theECG may indicate a certain cardiac abnormality (e.g., tachycardia) whichmay or may not be a clinical urgency. When the body compositionparameters indicate a rising amount of fluid in the lung(s), thecombined analysis may indicate that the tachycardia is causing improperpumping by the heart, leading to the fluid buildup in the lungs. Thetachycardia may be treated accordingly, for example, by a suitableelectrical pattern.

Optionally, the impedance-related parameter of a certain electrode(s) ofthe feeding tube is analyzed to identify whether the certainelectrode(s) is in contact with the LES. The contact between the certainelectrode and the LES denotes that the feeding tube is in a targetlocation. When the feeding tube is in the target location, theelectrodes on the feeding tube are located at their respective targetpositions for obtaining ECG measurements at target views of the heart.The ECG measurements obtained at the target views may increase accuracyof the analysis for determining likelihood of cardiac abnormality.

At 1922, instructions may be generated based on the analysis of the ECGand/or impedance-related parameters, for example, for execution by thecontroller and/or other computing devices and/or other controllers. Theinstructions may be for treatment of the subject.

Optionally, the instructions are for applying an electrical pattern fortreatment of the abnormal cardiac condition detected based on theanalysis of ECG (and/or other impedance-related parameters). Theelectrical pattern may be selected according to the determined abnormalcardiac condition.

The electrical pattern may be applied using the electrode(s) located onthe feeding tube, optionally from the same electrode(s) on the feedingtube from which the ECG measurement is sensed. The electrical patternmay be applied by a single electrode, or multiple electrodes, forexample, when a respective ECG is obtained from a respective electrode.For example, for the case of multiple electrodes, the electrical patternfor each electrode may be determined (e.g., computed) in order to obtaina synergistic effect for treatment of the heart, and/or in order toreduce the energy of the current applied to the heart at one location bydelivering lower energy current from multiple different locations.

Optionally, electrode(s) are selected for applying the electricalpattern. Certain selected electrodes may be activated, for example, byexpanding the expandable element (e.g., inflating a balloon on which theelectrode(s) is located) for contacting the inner surface of theesophagus. Such electrode(s) may be selected for applying the electricalpattern at selected regions, for example, higher up along the esophagus(from the LES) to target the atria and/or lower down the esophagus(closer to the LES) to target the ventricle(s). The electrical patternmay be applied when the electrode is in contact with the inner surfaceof the esophagus. The expandable element may be contracted (e.g., theballoon is deflated) after the electrical treatment.

Exemplary electrical patterns include: (i) Defibrillation electricalpattern, for example, for treating the cardiac abnormality ofventricular fibrillation (VF) and/or ventricular tachycardia (VT). (ii)Cardiac pacing electrical pattern, for example, for treating the cardiacabnormality of abnormal heart rate and/or block in electrical conductionin the heart. (iii) Cardioversion electrical pattern, for example, fortreating the cardiac abnormality of cardiac arrhythmia convertible tonormal sinus rhythm.

Optionally, the electrical pattern applied via the electrode(s) of thefeeding tube has significantly less power (e.g., lower amplitude pulse)in comparison to an electrical pattern that would otherwise be appliedin a standard approach (e.g., using a standard defibrillator and/orelectrodes for cardioversion) via extracorporeal electrodes to a skinsurface of a chest of the subject. For example, the electrical patternapplied via the electrode(s) of the feeding tube has a power of lessthan about 40, or 50, or 60 Joules, in comparison to standard approachesthat apply the electrical pattern via extracorporeal electrodes to thechest, in the range of about 100 to 500 Joules. The lower energyelectrical pattern applied by the electrodes of the feeding tube mayobtain the same treatment effect as a higher energy electrical patternapplied by extracorporeal electrodes applied to the chest in a standardapproach.

Alternatively or additionally, instructions are generated according tothe ECG measurement obtained from the electrode(s) of the feeding tubeand/or the impedance-related parameters, for adapting feeding and/ormedication of the subject by a feeding controller that delivers feedingmaterials via the feeding tube. For example, the type of feedingmaterial, the rate of feeding material, the composition of the feedingmaterial, supplements to the feeding material (e.g., protein), and/ordelivered water, may be adjusted according to the ECG measurementsand/or impedance-related parameters. For example, subjects with certaincardiac abnormalities may benefit from certain nutritional supplements,for example, extra potassium and/or magnesium.

Optionally, the instructions are for halting the feeding of the subject,for example, feeding is halted when an abnormal cardiac condition isdetected. The subject may be treated for the cardiac condition usingelectrical patterns applied via the electrode(s) of the feeding tube, inresponse to the halting of the feeding. The halting of the feedingduring application of the electrical pattern may help reduce risk ofvomiting and/or reflux, which may lead to aspiration pneumonia and/orasphyxiation.

Optionally, the instructions are for generating an indication, forexample, a presentation on a display, indicating a differentiationbetween gastric reflux and a cardiac abnormality. For example, for apatient experiencing chest pain, the pain may be due to reflux, or maybe due to a heart attack. The differentiation between gastric reflux andthe cardiac abnormality may be performed by analyzing theimpedance-related parameters computed from impedance measurements of theelectrode(s) of the feeding tube to detect whether gastric reflux ispresent in the esophagus, and/or by analyzing the ECG measurementsobtained from the electrode(s) of the feeding tube to detect whether thecardiac abnormality is present.

Alternatively or additionally, the instructions are for generating forexecution by a mechanical ventilator that mechanically ventilates thepatient, for adjustment of a mechanical ventilation pattern applied tothe patient for treating a respiratory abnormality. The respiratoryabnormality may be detected based on an analysis of a combination of theECG measurement and breathing parameter(s) (i.e., impedance-relatedparameters) to determine likelihood of a combined cardiac abnormalityand/or respiratory abnormality. For example, tachycardia leading toinsufficient blood pumping may lead to fluid buildup in the lungs, whichmay lead to the patient having difficulty breathing. The patient may beprovided with additional oxygen by the mechanical ventilator and/or thetachycardia may be treated with suitable electrical patterns. Examplesof processes for adjusting the mechanical ventilator based on impedancemeasurements obtained from electrode(s) on a feeding tube are described,for example, with reference to U.S. Publication No. 2019-0083725, by thesame inventors as the present application.

The generated instructions may be executed by the respective controllerand/or computing device, for example, for treatment of the abnormalcardiac condition of the subject by electrical patterns.

At 1924, one or more of 1906-1924 are iterated, for continuously (and/orsequential time interval) monitoring for cardiac abnormalities of theheart of the subject (i.e., via ECG measurements obtained fromelectrode(s) on the feeding tube) and/or treatment of the cardiacabnormality (i.e., via the electrode(s) on the feeding tube) and/ormonitoring impedance-related parameters and/or generating suitableinstructions, while the patient is being fed via the feeding tube, asdescribed herein.

The iteration(s) may be performed after the electrical pattern isapplied, in order to monitoring the ECG to determine whether thetreatment is effective or not. When the treatment is non-effective, thesame treatment may be re-applied, the previous treatment may be adjusted(e.g., increase power), and/or a new treatment may be selected (e.g.,new electrical pattern).

The monitoring of the contact between the certain electrode(s) of thefeeding tube and the LES may be iteratively performed for confirmingcontinuous contact between certain electrode(s) and the LES during themeasurements of the ECG.

Reference is now made to FIG. 20, which is a flowchart of an exemplaryprocess of monitoring a heart of a subject using electrocardiogram (ECG)measurements and/or monitoring for reflux using electrodes located on afeeding tube positioned in the esophagus, in accordance with someembodiments of the present invention. Features of the method describedwith reference to FIG. 20 may correspond to, be combined with, and/or besubstituted with features described with reference to FIG. 19. Thefeatures of the methods described with reference to FIG. 20 may beimplemented by components of system 100 described with reference to FIG.1, and/or features of implementations described with reference to FIGS.2-19. For example, by a controller implemented as computing device 104that includes memory 106 storing code 106A that when executed byprocessor(s) 102, causes processor(s) 102 to execute features of themethod described with reference to FIG. 20.

At 2002, reflux is monitored by impedance sensing at the electrode(s)located on the feeding tube located in the esophagus, as describedherein. A current, optionally an alternating current at a selectedfrequency, is applied to the electrode(s) on the feeding tube. Voltageis sensed at the electrode(s) on the feeding tube. Impedance is computedfrom the applied current and sensed voltage.

At 2004, an evaluation may be performed to determine whether ECG is tobe measured, by determining whether it is currently an ECG sample time.

When it is not currently ECG sample time, 2002 is iterated forcontinuously and/or repeatedly monitoring for reflux. When it iscurrently ECG sample time, the process continues to 2006.

At 2006, reflux sensing is stopped, by stopping the injection of currentinto the electrode(s) on the feeding tube.

At 2008, ECG is monitored at the electrode(s) on the feeding tube, bysensing voltage at the electrode(s) on the feeding tube when no currentis being injected into the electrode(s) on the feeding tube.

At 2010, the ECG measurements may be analyzed to determine whether acardiac abnormality is present. The analysis may be performed, forexample, automatically (e.g., based on a set of rules, a trainedclassifier, and/or other approaches), and/or manually (e.g., presentingthe ECG on a display, and a user enters an indication of whether thecardiac abnormality is present).

When according to the analysis, the ECG measurements are determined tobe indicative of normal and/or presence of a cardiac abnormality beingunlikely, 2002-2010 are iterated. Alternatively, when according to theanalysis, the ECG measurements are determined to be indicative oflikelihood of the cardiac abnormality being present, the processcontinues to 2012.

At 2012, a suitable cardiac correcting activity is selected according tothe ECG measurements, for example, as described herein. The suitablecardiac correcting activity may be a certain electrical pattern, forexample, defibrillation, pacing, and inversion.

At 2014, the selected cardiac correcting activity, optionally theselected electrical pattern, is applied to the subject using theelectrode(s) on the feeding tube for treating the cardiac abnormality.The same electrode(s) used to measure ECG may be used for applying theelectrical pattern. Alternatively, different electrode(s) on the feedingtube may be used for applying the electrical pattern and measuring ECG.Alternatively, some electrodes may be used for both measuring ECG andapplying the electrical pattern and other electrodes are used only forECG and others only for applying the electrical patterns.

At 2016, the process iterates from 2008 to monitor ECG to determinewhether the applied electrical activity successfully treated the subject(2010) or whether additional treatment is to be provided (2012-2014).

Reference is now made to FIG. 21, which is a flowchart of an exemplaryprocess of monitoring a heart of a subject using electrocardiogram (ECG)measurements and/or monitoring for reflux and/or measuring bodycomposition (e.g., lung fluid) using electrodes located on a feedingtube positioned in the esophagus, in accordance with some embodiments ofthe present invention. Features of the method described with referenceto FIG. 21 may correspond to, be combined with, and/or be substitutedwith features described with reference to FIG. 19 and/or FIG. 20. Thefeatures of the methods described with reference to FIG. 21 may beimplemented by components of system 100 described with reference to FIG.1, and/or features of implementations described with reference to FIGS.2-20. For example, by a controller implemented as computing device 104that includes memory 106 storing code 106A that when executed byprocessor(s) 102, causes processor(s) 102 to execute features of themethod described with reference to FIG. 21.

At 2102, reflux is monitored by impedance sensing at the electrode(s)located on the feeding tube located in the esophagus, for example, asdescribed herein and/or with reference to 2002 of FIG. 20.

At 2104, an evaluation may be performed to determine whether ECG is tobe measured, for example, as described with reference to 2004 of FIG. 20(e.g., by determining whether it is currently an ECG sample time) orwhether body composition sampling (e.g., lung fluid) is to be estimated(e.g., by determining whether it is currently a body compositionsampling time).

When it is not currently ECG sample time, 2102 is iterated forcontinuously and/or repeatedly monitoring for reflux. When it iscurrently ECG sample time, the process continues to 2106. Alternatively,when it is currently body composition sampling time, the processcontinues to 2020.

At 2106, reflux sensing is stopped by stopping the injection of current,for example, as described herein and/or with reference to 2006 of FIG.20.

At 2108, ECG is monitored, for example, as described herein and/or withreference to 2008 of FIG. 20.

At 2110, the ECG is analyzed to determine whether the ECG denotes normaland/or likelihood of no cardiac abnormality, or whether the ECG denotesabnormal cardiac activity, for example, as described herein and/or withreference to 2010 of FIG. 20.

At 2112, cardiac correcting activity (e.g., electrical patterns) isselected, for example, as described herein and/or with reference to 2012of FIG. 20.

At 2114, the selected cardiac correcting activity is applied, forexample, as described herein and/or with reference to 2014 of FIG. 20.

The process then iterates from 2102.

Alternatively, at 2020, reflux sensing is stopped, for example, asdescribed herein and/or with reference to 2006 of FIG. 20. It is notedthat for body composition monitoring, the injection of current may becontinued. Current may be adjusted, for example, a different frequencymay be selected for the alternating current.

At 2022, body composition is monitored by computing impedance based onthe selected frequency of the injected current and sensed voltage, asdescribed herein. Body composition may be monitored for a body segmentthat includes the electrode(s) on the feeding tube, for example, thelungs and/or lobes of the lungs, for example, for measuring lung fluidtherein, as described herein.

At 2024, the body composition may be analyzed to determine whether acardiac abnormality is present. The body composition may be analyzed incombination with the ECG measurement, for example, as described herein.For example, a cardiac abnormality and an increase in lung fluid maydenote a clinically significant condition that requires immediatetreatment.

The analysis may be performed, for example, automatically (e.g., basedon a set of rules, a trained classifier, and/or other approaches),and/or manually (e.g., presenting the ECG and/or body composition valueson a display, and a user enters an indication of whether the cardiacabnormality is present).

When according to the analysis, the body composition measurements (andoptionally in combination with ECG measurements) are determined to beindicative of likelihood of the cardiac abnormality being present, theprocess continues to 2026.

At 2026, a suitable cardiac correcting activity may be selected andapplied, for example, as described with reference to 2112-2114.

The process then iterates from 2102.

The descriptions of the various embodiments of the present inventionhave been presented for purposes of illustration, but are not intendedto be exhaustive or limited to the embodiments disclosed. Manymodifications and variations will be apparent to those of ordinary skillin the art without departing from the scope and spirit of the describedembodiments. The terminology used herein was chosen to best explain theprinciples of the embodiments, the practical application or technicalimprovement over technologies found in the marketplace, or to enableothers of ordinary skill in the art to understand the embodimentsdisclosed herein.

It is expected that during the life of a patent maturing from thisapplication many relevant electrodes will be developed and the scope ofthe term electrode is intended to include all such new technologies apriori.

As used herein the term “about” refers to ±10%.

The terms “comprises”, “comprising”, “includes”, “including”, “having”and their conjugates mean “including but not limited to”. This termencompasses the terms “consisting of” and “consisting essentially of”.

The phrase “consisting essentially of” means that the composition ormethod may include additional ingredients and/or steps, but only if theadditional ingredients and/or steps do not materially alter the basicand novel characteristics of the claimed composition or method.

As used herein, the singular form “a”, “an” and “the” include pluralreferences unless the context clearly dictates otherwise. For example,the term “a compound” or “at least one compound” may include a pluralityof compounds, including mixtures thereof.

The word “exemplary” is used herein to mean “serving as an example,instance or illustration”. Any embodiment described as “exemplary” isnot necessarily to be construed as preferred or advantageous over otherembodiments and/or to exclude the incorporation of features from otherembodiments.

The word “optionally” is used herein to mean “is provided in someembodiments and not provided in other embodiments”. Any particularembodiment of the invention may include a plurality of “optional”features unless such features conflict.

Throughout this application, various embodiments of this invention maybe presented in a range format. It should be understood that thedescription in range format is merely for convenience and brevity andshould not be construed as an inflexible limitation on the scope of theinvention. Accordingly, the description of a range should be consideredto have specifically disclosed all the possible subranges as well asindividual numerical values within that range. For example, descriptionof a range such as from 1 to 6 should be considered to have specificallydisclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numberswithin that range, for example, 1, 2, 3, 4, 5, and 6. This appliesregardless of the breadth of the range.

Whenever a numerical range is indicated herein, it is meant to includeany cited numeral (fractional or integral) within the indicated range.The phrases “ranging/ranges between” a first indicate number and asecond indicate number and “ranging/ranges from” a first indicate number“to” a second indicate number are used herein interchangeably and aremeant to include the first and second indicated numbers and all thefractional and integral numerals therebetween.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable subcombination or as suitable in any other describedembodiment of the invention. Certain features described in the contextof various embodiments are not to be considered essential features ofthose embodiments, unless the embodiment is inoperative without thoseelements.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims.

It is the intent of the applicant(s) that all publications, patents andpatent applications referred to in this specification are to beincorporated in their entirety by reference into the specification, asif each individual publication, patent or patent application wasspecifically and individually noted when referenced that it is to beincorporated herein by reference. In addition, citation oridentification of any reference in this application shall not beconstrued as an admission that such reference is available as prior artto the present invention. To the extent that section headings are used,they should not be construed as necessarily limiting. In addition, anypriority document(s) of this application is/are hereby incorporatedherein by reference in its/their entirety.

What is claimed is:
 1. A system for monitoring a heart of a subject andmonitoring parameters based on impedance measurements of the subject,comprising: a feeding tube for insertion into a distal end of anesophagus of the subject; at least one electrode disposed on a distalend of the feeding tube at a location such that at least one electrodeis located at the distal end of the esophagus of the subject when inuse; a controller that performs, while the feeding tube is in located inthe esophagus and feeding is delivered to the subject via the feedingtube, in a plurality of iterations: continuously measuring voltage atthe at least one electrode of the feeding tube; applying at least onealternating current between the at least one electrode of the feedingtube and at least one other electrode; computing at least one impedancemeasurement from the at least one electrode of the feeding tubeaccording to the applied at least one alternating current and themeasured voltage; computing at least one impedance-related parameterbased on the at least one impedance measurement; terminating theapplication of the at least one alternating current; obtaining anelectrocardiogram (ECG) measurement based on the voltage measured at theat least one electrode of the feeding tube; and providing the at leastone impedance-related parameter and the ECG measurement.
 2. The systemof claim 1, wherein the controller further performs: analyzing the ECGmeasurement to determine an indication of cardiac abnormality; andapplying via the at least one electrode of the feeding tube, anelectrical pattern selected for treating the cardiac abnormality.
 3. Thesystem of claim 2, wherein the at least one electrode of the feedingtube comprises a plurality of electrodes, and analyzing comprisesanalyzing each respective ECG measurement by each respective ECGelectrode, and wherein the controller further performs: selecting arespective electrical pattern based on the analysis of each respectiveECG measurement; and applying by each of the plurality of electrodes ofthe feeding tube, the respective electrical pattern for treating thecardiac abnormality.
 4. The system of claim 2, wherein the electricalpattern is selected from the group consisting of: defibrillationelectrical pattern for treating the cardiac abnormality of ventricularfibrillation (VF) and/or ventricular tachycardia (VT), cardiac pacingelectrical pattern for treating the cardiac abnormality of abnormalheart rate and/or block in electrical conduction in the heart, andcardioversion electrical pattern for treating the cardiac abnormality ofcardiac arrhythmia convertible to normal sinus rhythm.
 5. The system ofclaim 2, wherein the electrical pattern applied via the at least oneelectrode of the feeding tube has significantly less power in comparisonto an electrical pattern applied via extracorporeal electrodes to a skinsurface of a chest of the subject.
 6. The system of claim 5, wherein theelectrical pattern applied via the at least one electrode of the feedingtube has a power of less than about 50 Joules when the electricalpattern applied via extracorporeal electrodes is about 100 to 500Joules.
 7. The system of claim 2, wherein the analyzing the ECGmeasurements to determine the indication of cardiac abnormality and theapplication of the electrical pattern are iterated in the plurality ofiterations.
 8. The system of claim 2, wherein the controller furtherperforms: in response to the determined indication of cardiacabnormality, generating instructions for execution by a feedingcontroller for halting the feeding of the subject via the feeding tube;and in response to the execution by the feeding controller for haltingof the feeding, performing the application of the electrical pattern. 9.The system of claim 1, wherein the at least one impedance-relatedparameter comprises a body composition of a body segment located betweenthe at least one electrode of the feeding tube and the at least oneother electrode located externally to a body of the subject, wherein thecontroller further performs: analyzing a combination of the ECGmeasurement and the at body composition to determine likelihood of acertain cardiac abnormality selected from a plurality of cardiacabnormalities; and applying via the at least one electrode of thefeeding tube, an electrical pattern selected to treat the certaincardiac abnormality.
 10. The system of claim 9, wherein the bodycomposition comprises lung fluid and the body segment comprises a lung.11. The system of claim 9, wherein the analyzing the ECG measurements todetermine the indication of cardiac abnormality and the application ofthe electrical pattern are iterated in the plurality of iterations. 12.The system of claim 1, wherein the at least one impedance-relatedparameter comprises at least one breathing parameter indicative ofrespiration effort of the subject, wherein the controller furtherperforms: analyzing a combination of the ECG measurement and the atleast one breathing parameter to determine likelihood of a combinedcardiac abnormality and respiratory abnormality; and at least one of:(i) applying via the at least one electrode of the feeding tube, anelectrical pattern selected to treat the certain cardiac abnormality;and (ii) generating instructions for execution by a mechanicalventilator that mechanically ventilates the subject, for adjustment of amechanical ventilation pattern applied to the subject for treating therespiratory abnormality.
 13. The system of claim 1, wherein thecontroller further: generates instructions for adapting at least one of:a feeding and a medication by a feeding controller delivered via thefeeding tube according to the ECG measurement.
 14. The system of claim1, wherein the controller further: analyzes the at least oneimpedance-related parameter to detect an indication of gastric reflux inthe esophagus occurring during a time interval; analyzes the ECGmeasurement to detect likelihood of no new cardiac abnormality developedduring the time interval; and generate an indication that differentiatesbetween gastric reflux and cardiac abnormality.
 15. The system of claim1, wherein the at least one electrode comprises a plurality of spacedapart electrodes located on the distal end portion of the feeding tube,wherein obtaining comprises obtaining a plurality of ECG measurements,each respective ECG measurement obtained a respective electrode of theplurality of electrodes, wherein each respective ECG measurement denotesa different orientation relative to a heart of the subject according tothe respective location of the respective electrode on the feeding tube;wherein the controller further performs: analyzing the plurality of ECGmeasurements from the plurality of spaced apart electrodes located onthe distal end portion of the feeding tube to determine an indication ofcardiac abnormality; and applying via the plurality of electrodes of thefeeding tube, a selected electrical pattern to treat the cardiacabnormality.
 16. The system of claim 1, wherein the controller furtherperforms: analyzing the at least one impedance-related parameter of theat least one electrode to identify that the at least one electrode is incontact with the lower esophageal sphincter (LES) of the subject;wherein the analyzing is performed during the plurality of iterationsfor confirming continuous contact between the at least one electrode andthe LES during the measurements of the ECG.
 17. The system of claim 1,wherein the at least one electrode comprises a plurality of spaced apartelectrodes location on the feeding tubes, the position of the pluralityof spaced apart electrodes selected to obtain ECG measurements at aplurality of target orientations relative to the heart when a certainelectrode is in contact with the LES.
 18. The system of claim 1, whereinthe at least one other electrodes comprises at least one extracorporealelectrode located externally of a body of the subject for contacting thebody of the subject.
 19. The system of claim 1, wherein the at least oneelectrode disposed on the distal end of the feeding tube comprises aplurality of electrodes disposed on the distal end of the feeding tube,wherein the at least one electrode comprises a first electrode of thefeeding tube and the at least one other electrode comprises a secondelectrode of the feeding tube.
 20. A method of monitoring a heart of asubject and monitoring parameters based on impedance measurements of thesubject, comprising: providing a feeding tube for insertion into adistal end of an esophagus of the subject; providing at least oneelectrode disposed on a distal end of the feeding tube at a locationsuch that at least one electrode is located at the distal end of theesophagus of the subject when in use; while the feeding tube is inlocated in the esophagus and feeding is delivered to the subject via thefeeding tube, in a plurality of iterations: continuously measuringvoltage at the at least one electrode of the feeding tube; applying atleast one alternating current between the at least one electrode of thefeeding tube and at least one other electrode; computing at least oneimpedance measurement from the at least one electrode of the feedingtube according to the applied at least one alternating current and themeasured voltage; computing at least one impedance-related parameterbased on the at least one impedance measurement; terminating theapplication of the at least one alternating current; obtaining anelectrocardiogram (ECG) measurement based on the voltage measured at theat least one electrode of the feeding tube; and providing the at leastone impedance-related parameter and the ECG measurement.
 21. A computerprogram product for monitoring a heart of a subject and monitoringparameters based on impedance measurements of the subject, comprisingprogram instructions which, when executed by a processor, cause theprocessor to perform, while a feeding tube is in located in a distal endof an esophagus of the subject and feeding is delivered to the subjectvia the feeding tube, in a plurality of iterations: continuouslymeasuring voltage by at least one electrode of disposed on a distal endof the feeding tube at a location such that at least one electrode islocated at the distal end of the esophagus of the subject when in use;applying at least one alternating current between the at least oneelectrode of the feeding tube and at least one other electrode;computing at least one impedance measurement from the at least oneelectrode of the feeding tube according to the applied at least onealternating current and the measured voltage; computing at least oneimpedance-related parameter based on the at least one impedancemeasurement; terminating the application of the at least one alternatingcurrent; obtaining an electrocardiogram (ECG) measurement based on thevoltage measured at the at least one electrode of the feeding tube; andproviding the at least one impedance-related parameter and the ECGmeasurement.